The term fear is firmly entrenched in both our technical vocabulary and the vernacular. It
little purpose to offer a precise definition for the present discussion, but some consideration of the
in which the term has been defined may be useful. For research purposes, conditioned fear typically
is defined operationally in terms of the environmental events that set the conditions for fear,
some behavioral or physiological index is frequently used to corroborate the effect. Irrespective
precision of this operational definition, the ultimate goal of the research (and, indeed, the choice
parameters that make up the operational definition) is to provide an experimental model that
the human conditions listed above. This remains a distant goal, but major developments within
areas of experimental psychology and psychopharmacology allow a reasonably coherent model to
The terms conditioned fear or learned fear underscore the importance of experience in
sources of fear. Some theorists claim that all fears are learned during the lifetime of the
those who argue for innate fears present a very short list of exemplars (e.g, fear of snakes, fear of
unsupported heights). In virtually all cases, the fear is based upon some consistent relationship
the environment and some painful or otherwise noxious stimulus. It is the understanding of these
environmental relationships that provides us with the experimental procedures to study fear and
The earliest experiments, and those which have become most important in our understanding
were done by Pavlov (1927). His reasons for conducting these
experiments were not to learn about
fear and anxiety, but rather to develop the laws for learning about environmental relationships.
important distinction was the one made between the unconditioned response (UR) and the
or conditional response (CR) of the organism. The UR is the direct response that is elicited by the
noxious stimulation. Examples put forth by Pavlov include the defensive salivation in response to
sour taste of acid, leg flexion in response to foot shock, and other motor responses to intense
stimuli such as a pin prick. Pavlov recognized the importance of the psychic (i.e., emotional)
component of this direct response to the strong stimulation and, more importantly, the ability of
emotional component to move forward in time and anticipate the occurrence of the painful
Pavlov studied this phenomenon in considerable detail, but the three paradigms shown in Figure 4-1
demonstrate the most important principles that he developed:
The delay conditioning procedure can also utilize long delays with somewhat different results.
procedure, the CS is gradually presented for longer and longer periods of time until there is
long delay between the onset of the CS and the occurrence of the painful US. Pavlov found that
animals not only could bridge this gap in time, but ultimately were able to appropriately delay the
occurrence of the CR until it just preceded the arrival of the US.
The trace conditioning procedure involves a brief presentation of the CS, a period of time
no stimulus is presented, and then the presentation of the painful stimulus. Under these
anticipatory responding is slower to develop and more fragile, but the success of the procedure
provided the necessary demonstration that the conditioned response could be based upon the
(trace) of a previous stimulus.
In summary, Pavlov developed the experimental procedures to study the important facts that
behaviors such as fear do not require the actual presence of an aversive event, but can be
a lawful fashion) by events that have reliably predicted the occurrence of aversive events. As we
see later, it is this separation in time of emotional behavior from the actual events that elicit the
response that forms the basis for the development (and treatment) of stress disorders.
Pavlov's experimental procedures involved the physical restraint of the subjects, thereby
types of anticipatory responses that could be made. The experimental procedures that evolved in
United States involve much less restraint and allow more global response patterns to be emitted.
of the more common parallels to Pavlov's unconditioned response places the subject (usually a rat
rather than a dog) in a long, narrow alleyway that has an electrified grid floor (see Fig. 4-2). The
subject can escape from this painful stimulation by running to the opposite end of the alley and
into the non-electrified goal area of the box. Note that the subject's behavior is
escaping from the aversive stimulation. Learning is evidenced by progressively faster running
This simple escape procedure is typically modified to include an initial warning signal (i.e., a
allows a brief period of time to reach the goal area before the shock (US) arrives. Thus, the rat
either avoid the shock by traversing the alley during the presentation of the CS or, failing that, can
escape the shock that follows several seconds later. For the philosophically myopic, the ability of
rat to rapidly learn to avoid the impending shock so readily was a problem: Was the rat
some behavior that was based upon some future set of events? Well, of course it was, but the
acceptance of this notion was aided greatly by the proposal of the so-called two factor theory of
Two factor theory
Some of the early experimentalists saw the distinction between classical and instrumental
as being too arbitrary, and suggested that instrumental conditioning may include a component of
classical conditioning (e.g., Mowrer, 1939). The two factor theory
suggests that avoidance behavior is
based upon a combination of classical (Pavlovian) conditioning and instrumental conditioning.
subject first learns the environmental relationships that exist according to the laws of
conditioning, for example, the onset of a light (CS) is reliably followed ten seconds later by the
shock (US) to allow the development of anticipatory fear. (Other stimuli such as handling, the
characteristics of the testing chamber, etc., can also serve as CSs). Once this anticipatory fear has
been established, the organism can learn the environmental contingencies that are
that certain responses are instrumental in terminating either the fear-producing CS or the actual
pain-producing US. Thus, the notion of conditioned fear becomes an important determinant in
selection of behavior, and the so-called avoidance responses are actually responses that escape
In the simple experimental procedures described above, the conditioned fear plays a straightforward, even positive, role in guiding the behavior of the organism. There are, however, a variety of situations in which the same fear response interferes with ongoing behavior and, as we will see shortly, contributes to the harmful physiological effects of stress. One of the early demonstrations of a learned fear response that is basically nonproductive was Watson and Rayner's (1920) somewhat infamous experiment with Little Albert. A few presentations of a white stuffed toy (CS) followed by a loud noise (US) resulted in a learned fear response that could be elicited by the presentation of the CS alone. In fact, this learned emotional response was elicited not only by the original stuffed toy, but by other similar white furry objects-- a phenomenon called stimulus generalization. Although the procedures and the underlying processes of learning are essentially identical to Pavlov's simple conditioning procedure, the resulting conditioned response seems less adaptive than leg flexion in a restraining harness. The conditioned fear in these types of situations can be maintained for long periods of time, perhaps indefinitely, through interaction with other behaviors. Individuals who have such fears (e.g., phobias) typically adopt behaviors (avoidance responses) that prevent or minimize contact with the fear eliciting stimuli. This not only results in undesirable restriction of unrelated activities, but also allows many situations that are only remotely related to elicit low levels of fear or anxiety in anticipation of approaches to the original stimulus.Conditioned emotional response
This interference with unrelated behaviors formed the basis for another experimental model
termed conditioned emotional response (CER) or conditioned suppression (cf., McAllister &
McAllister, 1971). In this procedure, some baseline behavior such as lever pressing for food
is established. After stable rates of responding have been attained, a long-lasting CS (e.g, a
tone) is presented and terminates with the presentation of a brief intense shock. After a few such
pairings of the tone and shock, the subject will suppress responding during the CS presentation,
though the food reward contingency is still in effect, and completely independent of the
pairings. The usual interpretation of this is that the tone elicits a conditioned fear response which
incompatible with feeding. This procedure has been used in countless experiments as the
situations in which conditioned fear interferes with other, unrelated behaviors. Ironically, the
influence of the CER situation can be attributed to the actual lack of relationship to
that is food rewarded.
The punishment procedure contrasts sharply with the noncontingent shock presentation that
characterizes the CER. Punishment procedures specifically deliver an aversive stimulus each time
particular response is made, and have the advantage of greatly narrowing the range of suppressed
behaviors, leaving most other behaviors unchanged. Another way of looking at this phenomenon
the behavior per se comes to serve as the CS which predicts shock. Other behaviors do not
shock and, hence, do not lead to the learned fear that suppresses ongoing activity.
Punishment procedures are not without problems. To the extent that the behavior in
strongly motivated, the delivery of punishment can lead to a situation of conflict. One of the most
widely used conflict procedures which will be referred to in several cases later, is the procedure
developed by Geller and Seifter (1960). This procedure combines
elements of the
experimental situations that have been described above. First, the subjects are trained to press a
to obtain some positive reinforcer such as food, which is usually presented on a variable interval
schedule of reinforcement. After behavior is well established, a long-lasting CS is presented.
the CER situation, this CS does not signal the actual delivery of a shock, but rather signals the
of a punishment contingency in which every response is accompanied by both food reward and a
shock. This situation provides a clear marker for the punishment contingency, and shock levels
food motivation can be varied to maximize or minimize the level of conflict.
Two way avoidance
Finally, it should be noted that conditioned fear can interfere with fear motivated behavior as
with positively reinforced behaviors. One situation in which this is especially salient is the
avoidance situation. In this task, a CS such as a light is presented in one end of an alley, followed
the delivery of foot shock. The subject can escape (or avoid) the shock by shuttling to the other
the alley. After a period of time, the CS is presented in the other end of the alley, and the subject
return to the original location in order to escape or avoid the shock. Thus, there is no actual safe
location, but rather the organism must learn that the CS signals the onset of "local" shock which
only be avoided by returning to yet another location in which shock already has been experienced.
particular importance in considering this type of behavior is that increases in the amount of fear
higher shock intensities) actually slows down the rate of learning (cf., Moyer
& Korn, 1964). The
conflict in this situation interferes with learning to such an extent that typical rats require dozens
hundreds of responses to learn the task, while many do not learn at all.
The experimental procedures described above, along with many variations, have been used
in basic research related to learning and the aversive control of behavior. Although it is an
oversimplification, these tasks bear a reasonably close relationship to the various categories of
psychiatrically important fears that may be encountered in the clinic.
The simple conditioning procedure can set the stage for both the normal, benign fears of
and the more debilitating phobias. The distinction lies primarily in the time course and severity of
conditioned fear, as well as the object of the fear. In many cases, the conditioned fear response is
weakly established and transient, owing to the lack of a consistent relationship with a strongly
stimulus. Such fears are of little consequence. However, a strongly based fear of a common
situations (e.g, elevators, bridges, cats, etc.) can be maintained indefinitely and even strengthened
time, owing to the individual's ability to avoid contact with the feared object.
In situations in which the object of the phobia cannot be avoided, the resulting influence on
comparable to that observed in the CER procedure. The fear that results from the presence of the
interferes with virtually all ongoing behaviors. This lack of behavior is not only debilitating in and
itself, but prevents the occurrence of behaviors that might normally lead to the extinction of the
The clinical etiology of compulsive behavior is considerably more complex, but many cases
their roots in simple Pavlovian conditioning. The disorder is complicated by the interaction of the
learned fear response with overt behavior. Just as the punishment procedure described above is
effective because the behavior itself comes to serve as a CS that signals an aversive consequence,
behaviors that are a part of the compulsive repertoire can serve both to elicit the fear and then to
reduce it, setting up a vicious cycle.
Vague or nonspecific anxieties are perhaps the most common form of debilitating fears. As
implies, there is frequently some degree of uncertainty about the actual source of fear.
these vague fears can build upon themselves, such that individuals begin to fear that certain
may lead to fear. In Pavlovian terms, this would be fear that anticipates the arrival of a CS that
an aversive event. In human terms, it is the "fear of fear itself" that seems to be particularly
The pattern of reactions described above can be elicited by a wide variety of situations, the
criterion being a situation that offers real or perceived danger. The physiological changes that
have clear, adaptive value by virtue of increasing the likelihood of successfully fleeing or fighting
aversive situation. Indeed, any local folklore contains at least a few anecdotes of nearly
feats that were accomplished under the influence of the sympathetic stress response.
The beauty of the adrenal stress response lies in the speed with which it prepares the organisms
action, but the resulting changes in physiology simply cannot be maintained for long periods of
Hans Selye looked beyond this immediate response to stress and made two very important
observations: (a) Long term exposure to stressful situations can deplete the organism's ability to
maintain the stress response, and (b) The pattern of these deleterious effects is independent of the
source of stress. Selye (cf., 1956) outlined a three-stage progression
responses to stress that he
termed the General Adaptation Syndrome:
Alarm, Resistance and Exhaustion. When a stressor is
first encountered, a series of responses is initiated in the autonomic nervous system, the immune
and other defenses to cope with the emotional, behavioral and physiological aspects of the
This is called the Stage of Alarm. The maintenance of this
reaction to the stressor, which includes
reparative processes such as fever regulation, tissue repair, control of inflammation, etc., is termed
Stage of Resistance. In some cases, the stressor
successfully countered, and the organism
enters the Stage of Exhaustion. In this stage, the
against the stressor begin to fail, metabolic
reserves are depleted, there is a general decline in physiological functions, and serious illness or
One of the most important of Selye's observations was that this is a general response that is
independent of the situation that initiates it. The three stages of the General Adaptation
be triggered by disease, injury, psychological stress, or some combination of these.
One of the common sources of trauma that can initiate the stress syndrome is that associated
surgical procedures. Even before the time of Selye, surgeons recognized the dual hazards of their
Death can result either as a direct effect of surgical complications, or as a result of surgical shock
not directly attributable to the success of the surgical procedure. The French surgeon, Henri
became interested in this phenomenon in the 1940's and undertook a program of clinical research
observation that was to have far reaching consequences for the treatment of stress related
(cf., Caldwell, 1970).
Laborit recognized that surgical trauma involved intense activation of the autonomic nervous system. Normally, the autonomic nervous system maintains bodily functions within fairly tight limits, automatically adjusting the organism's physiological needs to fit the ongoing requirements. These routine adjustments are primarily the responsibility of the parasympathetic, or vegetative, division of the autonomic nervous system (see Fig. 4-4). But in times of severe stress, these systems can run amok, producing bodily changes that are counterproductive, leading to the life threatening condition that is commonly referred to as shock. Attempts to treat the stress may, in some cases, contribute further to the stress. Laborit stated this with an eloquence that survives translation:
"In fact, perfect lytics are not yet at our disposal and even if one existed, it probably would be effective only in large doses. In that case, an injection of the drug would increase the stress that, when it attains a certain level, elicits organic defense reactions that are quite contrary to our fixed goals (prevention or mitigation of those exaggerated reactions that defend our invariant inner milieu that guarantees liberty but not always life.)
(trans. by Caldwell, 1970, p. 29)
Laborit was not alone in challenging Cannon's sympathetic model of stress. In a paper that
originally published in 1942, Cannon had suggested that massive
overreaction of the adrenal system
could lead to Voodoo death (sudden death that was caused by emotional rather than physical
The most impressive evidence against this model came from an elegant series of experiments
by a psychologist, Curt Richter, who investigated this curious phenomenon of sudden death.
Richter's initial experiments bore little or no relationship to the stress syndrome. He had
concerned that the methodical inbreeding of the albino laboratory rat had rendered it too weak to
as an adequate model subject. He attempted to prove his hypothesis by showing that the albino
physically weak when compared to its wild, Norway rat counterpart. He developed an endurance
that involved swimming in a circular tank, equipped with a sort of whirlpool in the center that
continuous swimming. The results of the first experiment were somewhat curious: At optimal
temperatures, most of the rats swam 60-80 hours, but a few died within 5-10 minutes. Why?
recalled an earlier observation in which a rat's whiskers (vibrissae) had been trimmed as part of
experiment. The rat began to behave strangely, and died about eight hours later!
suspected that this might have been related to stress, and clipped the whiskers of 12 rats before
the swim test. Three of the 12 died within minutes, but the remaining nine swam 40-60 hours.
contrast, all wild rats tested in the same way died within minutes and many of them
even without the
Richter searched beyond the superficial aspects of these results. He suspected that this
exhaustion and death of the wild rats might be related to the Voodoo death phenomenon, as
by Cannon. The prediction to be made by Cannon's sympathetic model was clear--the release of
adrenaline should cause the heart to beat faster and faster until it no longer had time to fill
beats, leading to death in systole (i.e, a contracted heart). The actual results were exactly
The heart rate of the wild rats became slower and slower, with the autopsy showing the heart to
completely engorged with blood. These results bore all the earmarks of a massive
Richter tested the notion that this was a parasympathetic response using two pharmacological
procedures. In one case, he administered mecholyl (a parasympathetic mimicker) to the albino
They quickly acquiesced to the swimming task and sank to the bottom, like the wild rats. In the
case, he administered atropine (a parasympathetic blocker) to the wild rats, which prevented the
sudden death in some, but not all of the rats tested. The combination of these results, summarized
figure 4-5 spun an irrefutable conclusion: The sudden death
Richter pursued the emotional causes of this stress syndrome. Is it possible that the normal,
sympathetic response to stress is replaced by a parasympathetic response under extreme
The rats' vibrissae provide a major source of information. Lacking this information in a hostile
environment such as the swimming tank, could render the situation hopeless, leading to this
parasympathetic response. But what about the wild rats? Richter suggested that they may also
the situation as hopeless simply because (being wild) it is more stressful to be handled, and they
never before been in captivity. To test this notion, he allowed several of the wild rats to sink to
bottom of the tank. Then, retrieving them from otherwise certain drowning, he placed them on
until they recovered, then put them back in the tank. After a few repetitions of this lifeguard
wild rats would swim for many hours. The conclusion, which seems valid, was that the wild rats
learned that the situation was not hopeless after all.
The results of Richter's experiments bring up several important points that go beyond the
1. A behavioral phenomenon can be blocked through the pharmacological blockade of
the target organ receptor. (Atropine prevented the sudden death in wild rats).
2. A behavioral phenomenon can be mimicked or exaggerated through the
pharmacological stimulation of the target organ receptor. (Mecholyl triggered the
sudden death in albino rats).
3. Manipulations that change the perception of the environment can either exaggerate a
behavioral phenomenon (as in the case of shaving the rats' vibrissae) or block a
behavioral phenomenon (as in the case of rescuing the wild rats).
4. The perception of the environment is an important determinant of the nature of
autonomic response to stressors.
The hallmark of stress disorders is the formation of ulcers. This condition has become
with demanding job situations such as executive positions, and with other situations that involve
exposure to stressful conditions. The superficial reason for ulcer formation is the release of
acids into an empty stomach. The presence of these digestive juices, along with some local
changes, lead to the digestion of the stomach lining itself, and can sometimes lead to an actual
through the stomach wall, a perforated ulcer. The real reasons for ulcer formation, however, can
traced back to the emotional responses that set the stage for this untimely release of digestive
Ulcers are far more than a clinical curiosity. They are painful and even life threatening to the
who are afflicted. Furthermore, they account for tremendous financial losses in terms of
and medical costs. The impact of this disorder has stimulated a great deal of research to
cause of the disorder and to develop pharmaceutical treatments for the disorder. Obviously, the
solution would be to eliminate the conditions that initiate the ulcerative process, and toward this
there has been considerable effort to develop an animal model of the stressful conditions that
hypersecretion of gastric acids.
The cornerstone of this effort was Brady's (1962) so-called
Monkey study. This study is
important for historical reasons, even though the basic conclusions drawn from the study were,
ultimately, shown to be exactly opposite to current knowledge in the area. Brady trained a group
monkeys to perform a free operant (Sidman) avoidance task which required that a lever be
avoid shock to the tail. If the monkeys allowed too much time to elapse before pressing the lever,
electrical shock was delivered to the tail. The executive monkeys spent each workday sitting in
restraining chair performing this task. The worker monkeys sat in a similar restraining chair with
electrodes attached to their tails, but the delivery of electrical shock was entirely dependent upon
executives' decisions. If the executive received a shock, so did the worker. Consistent with the
predictions, the executive monkeys eventually developed gastric ulcers and the worker monkeys
not. Unfortunately, these results support the wrong conclusions because of a combination of
procedural details and flaws in experimental procedure. We will return to an analysis of these
The triad design
The most comprehensive behavioral research in this area has been done by Weiss and his associates
(e.g., 1968; 1981). These experiments, utilizing rats as subjects, have reached conclusions
diametrically opposed to those of Brady, but at the same time confirm the actual results of those
studies. Although the testing procedures have varied over the years, most of these experiments
utilized the apparatus and procedures that are shown in Figure 4.6 and
The rats were placed into small restraining cages with electrodes attached to their tails. A
located immediately in front of the rats, could be turned with their front feet. In the prototype
there were three testing conditions (a triad) that differed in terms of the degree of interaction each
had with the shock. Although each of these experiments involved many rats, the testing was
conducted in triads so that the environmental conditions of the rats were interdependent. The
experiments will be described separately to demonstrate the major conclusions that were reached
Weiss' research group.
Control of stressors
The most critical set of experiments involved an assessment of the importance of control over the environment. The test triad in these experiments was exposed to the following conditions:
(a) Escapable: Electric shock was delivered to the rat's tail at random intervals. Once the shock was begun, it was programmed to continue until the rat turned the wheel with its front paws. Thus, the rat had control over the termination of the shock.
(b) Inescapable: This rat's tail was connected to the same shock source as the experimental rat. Although it could turn the wheel, the wheel did not influence the shock. Shock termination only occurred when the experimental animal successfully turned it off. This link to the behavior of another subject is referred to as a yoked control procedure.
(c) Control: This rat was maintained in the restraining cage for the duration of
experiment, but was
not exposed to the electric shock.
The results of these experiments were clear: The rats in the yoked control condition
ulcers, the other two groups did not. Contrary to the results of Brady's experiments, the subjects
were in charge of shock decisions were the ones that developed the ulcers. However, if these
are described in slightly different language, they seem to make a lot more sense. The rats that had
control (i.e., mastery) over the shock were less stressed than those which were at the mercy of
Prediction of stressors
A second set of experiments extended Weiss' analysis of the conditions that lead to ulcers. In
experiments the following conditions formed the test triad:
(a) Signaled: A signal (CS) was presented at random intervals, followed by a
(b) Unsignaled: Again, the rats in this condition received shocks that were
by the experimental group. The distinguishing feature was that they did not receive the CS that
the impending shock.
(c) Restrained Only: These rats received neither the CS nor the shock.
The results of these experiments began to support a more general notion of mastery over the
environment. Once again, it was the subjects in the yoked control condition that developed the
ulcers. The experimental animals received the same shock, but apparently the mere knowledge of
when the shock was going to be delivered reduced the stress. They developed very few ulcers.
Presence of Conflict
A third set of conditions begins to come closer to the human conditions that are likely to engender ulcer formation. This is the presence of conflict, which Weiss modeled with the following triad:
(a) Signaled escape: A signal (CS) for impending shock was presented at random intervals, as in the experiments investigating the importance of prediction. However, these rats also had control over the shock, in that turning of the wheel could either terminate the shock or, if it occurred during the CS, actually avoid the shock altogether.
(b) Conflict: These rats were exposed to conditions that were identical to those of the experimental rats, except that on some trials, the wheel turning response itself was punished with electric shock.
(c) Restrained Only: Again, these rats were simply restrained for the duration of
The rats in the signaled escape condition of this experiment were completely free from ulcers.
suggested by the separate experiments above, the presence of both prediction and control negates
formation of ulcers. The presence of conflict, however, led to severe ulceration. In some sense, it
would appear to be better to have no control or prediction at all, than to have these available but
inconsistent. Figure 4-7 summarizes these results.
The results of these experiments support a remarkable conclusion: Noxious stimuli are not
stressful. In all of the experiments above, the experimental group received shock that was
that of the second group in terms of the interval of presentation, the intensity and the duration.
critical factor was not the presence or absence of electric shock, but rather the presence or
what we might call a particular "interpretation" of the electric shock. Prediction, control, and the
absence of conflict are the three factors that prevent noxious stimuli from becoming stressors.
Why did Brady get the opposite results? The answer lies within Weiss' experiments. Animals
exposed to shock (even though it is neither predictable nor controllable) will not develop ulcers
the frequency of occurrence is fairly high--an occasional brief shock is simply not stressful enough
cause a problem. In Brady's experiments, the executive monkeys were skilled enough to prevent
shock from occurring, so the worker monkeys were not exposed to very many shocks. There are
several reasons for the development of ulcers in the executive monkeys. Even though they had
the free operant situation requires constant vigilance, and there is no external CS to predict the
The sessions lasted for hours and the constant requirement of timing responses to avoid shock is
obviously stressful. Another important factor was that all the monkeys were initially
executive condition, and when about half of the subjects had mastered the task, the remaining
were switched to the worker condition. This biased selection of subjects made it even more likely
the executive group would develop ulcers, because later studies with rats have shown (for reasons
are not clear) that rats which learn avoidance responses quickly are also more prone to develop
All of this is consistent with the conditions that lead to ulcers in the human environment. The
and control of corporate executives is illusory. Although they are required to make decisions, the
environment is sufficiently complex that the outcome of the decisions is uncertain and
punished (hence, conflict). It is the menial laborer who has prediction and control by virtue of
tasks, scheduled daily activities, and known outcomes for most work related behavior. Not that
individuals are immune to ulcers, but the source of the conditions that lead to the ulcers is more
be found in the home or social environments of these individuals than in their work places.
The experimental procedures that result in ulcer formation fit into a larger context of
produce aberrant responding of the autonomic nervous system. The procedures that produce
not appear, on the surface, to be life threatening. When compared to the trauma of either a
procedure or Richter's swimming task, the lack of prediction or control over electric shock would
to be rather benign. Yet, the common emotional fabric of all of these is the hopelessness and lack
control of the environment. It is the behavioral interpretation of the environment (be
that leads to an autonomic imbalance in the direction of parasympathetic over-responding.
One of the effects of surgery (or other tissue damage) is the release of histamine, which is also
stimulator of some autonomic target sites. (A common example is the redness of the skin that
through local vascular responses when it is scratched.) This response to tissue damage (which
called "silent pain") occurs under anesthesia as well as when an individual is awake, adding to the
complications of surgery. By the late 1940's, several antihistamine compounds had been
and were being used with some degree of success to control surgical shock. Laborit was
what he termed the perfect lytic compound--a drug that would stabilize the autonomic nervous
and, in a sense, "dissolve" the patients' fears. He was somewhat pessimistic, however, because he
recognized that a heavy dosage of a drug is itself a stressor that can trigger the stress syndrome
Despite his pessimism, Laborit saw hope for a lytic compound in one of the antihistamines,
promethazine. In addition to its effects of stabilizing the peripheral autonomic nervous system,
also had mild effects on the central nervous system, resulting in a sort of indifference to the
environment. This indifference was in contrast to a troublesome sedative and hypnotic side effect
accompanied many of the other antihistamine compounds. Caldwell
relates an instance in
which one of Laborit's patients ran through a red light, even though he was not noticeably drowsy
inattentive. Working with a biochemist in a drug company (Specia), Laborit guided the
antihistamine molecules to bring about maximal central activity, irrespective of action in the
Finally, on December 11, 1950 the drug that was to launch modern psychopharmacology was
synthesized: That drug was chlorpromazine.
Literally thousands of experiments have been done to test the effectiveness of chlorpromazine,
acid test in terms of animal experiments would be Richter's swimming test. If the drug is truly
as an autonomic stabilizer, then it should prevent the sudden, parasympathetic death of rats in the
test: It did.
The first patient to be treated with chlorpromazine was a young man who had a history of
psychotic behavior. He had entered the Val-de-Grace Hospital in September of 1949 and
shock treatments. In February of 1951, he returned to the hospital and received 24 additional
treatments (both insulin and electric). In January of 1952, he was given 50 mg of chlorpromazine
immediately became calm. After seven hours, his agitation returned, but subsided again with a
dosage of the drug. Gradually, the drug's effectiveness lasted longer and longer, and the patient
released after 20 days.
It is almost impossible to overestimate the impact of this drug and the related phenothiazines
and treatment of psychiatric patients. Prior to the advent of chlorpromazine, psychiatric patients
rarely released from the hospital. The chronic, in-patient population was ballooning, and the care
bordered on the barbaric. Straight jackets and restraining chairs were used routinely for the
of patients and staff alike. Electric and insulin shock treatments were common procedure. There
no alternatives and the patients were more likely to get worse than to get better. Chlorpromazine
literally freed the psychiatric patients from their bondage. It effectively reduced their fears and
to the point that restraining devices were unnecessary. The drug was not habit forming and
was minimal. Most importantly, the patients were not asleep as they had been with barbiturates
other sedative/hypnotics. They retained their ability to interact with their environment, but were
indifferent to the stressors.
With the advent of chlorpromazine, patients went home. As shown in Figure 4-9, their is a dramatic
reversal of the in-patient population beginning in 1952. The savings in dollars has been estimated
billions, and the savings in human suffering is incalculable. The patients were not, to be accurate,
But the drug allowed them to regain a sufficiently cogent interaction with their environment to be
care of safely in a family setting.
The details of the action of the phenothiazines will be presented more fully in Chapter 6, but it
important to consider the development of the drugs at this point because of the impact they had
investigation of the pharmacology of stress. The immediate success of chlorpromazine made drug
therapy in psychiatry a reality, and spawned a major search within the pharmaceutical industry for
more, if not better, compounds. As a result, chlorpromazine is simply the prototypical example of
group of chemicals known as phenothiazines, which are sometimes referred to as neuroleptics (in
reference to their autonomic stabilizing effects), as major tranquilizers (in reference to the
deconditioning effects), and as antipsychotics (encompassing both of the above and the fact that
are especially effective in treating this patient population).
Antianxiety Drugs (Benzodiazepines)
The success of chlorpromazine in treating psychotic patients led to an intense search for other
would have a calming influence, particularly on the fears and anxieties that occasionally interfere
lives of otherwise normal individuals. The phenothiazines were, to some extent, too much of a
thing. The emotional flattening and autonomic side effects were reasonable alternatives to
episodes, but seemed like a high price to pay for the treatment of patients who were, perhaps, a
nervous about their new job. Consequently, the search for new drugs was aimed toward
that would calm the day-to-day anxieties while having only minor side effects. The most
drugs produced by this effort was a class of compounds known as the benzodiazepines, of which
chlordiazepoxide (Librium) and diazepam (Valium) are the most commonly prescribed.
These compounds are variously referred to by the name of the chemical class, as minor
and as antianxiety compounds. They are useful and widely prescribed to reduce the tensions and
anxieties associated with job and family situations, as well as to relieve or prevent associated
such as muscle tension and headaches.
The screening of drugs that are potentially useful in treating stress related disorders virtually
animal models. The financial costs, time requirements, and potential dangers of clinical tests with
humans all require that the initial stages of testing be done with animal tests. As a result, there are
several testing procedures that are useful in categorizing the drugs and to provide further
about the nature of the behavioral changes produced by the drugs' actions on the brain.
In the discussion above, it was pointed out that one of the major effects of chlorpromazine
something termed Pavlovian deconditioning. The results of animal tests confirm this notion, and
worthwhile to directly compare the effects the phenothiazines and the benzodiazepines on these
tests. In appropriate dosages, chlorpromazine (and other phenothiazines) can reduce avoidance
responding (i.e., conditioned responses to fear), while leaving escape behavior intact (cf., Cook &
Sepinwall, 1976; see Fig. 4-10A).
This selective effect on these two closely related responses provides an excellent initial screen
that are likely to share the antipsychotic effects of chlorpromazine in the clinic. By contrast, the
anti-anxiety compounds reduce avoidance behavior only in dosages that are sufficiently large to
escape responding (Fig. 4-10B). This nonspecific effect can be
by several different classes of
drugs (e.g., those that simply impair movement), so this task has little or no utility in screening for
compounds that might serve as anti-anxiety drugs.
There is, however, a task that provides a sensitive screen for potential antianxiety drugs.
seem to be uniquely effective in changing performance in the Geller-Seifter punishment procedure
was described earlier. Initially, this test was used to demonstrate the
specific effects of barbiturate
drugs, because these were the most widely prescribed drugs for the treatment of anxiety. The
response to punished responding following barbiturate administration is mirrored by the
of chlordiazepoxide and other benzodiazepines In this test, the animals that have been treated
drug show perfectly normal behavior patterns in the food rewarded portion of the schedule, but
markedly different from control animals during the punishment portion. Whereas normal rats will
responding when the signal for shock plus food is presented, rats that have been treated with one
anti-anxiety compounds are released from this suppressive effect and continue their high rate of
The Geller-Seifter screening procedure is especially important because it discriminates the
compounds from other classes of drugs. Chlorpromazine and other antipsychotic compounds are
ineffective in this procedure. General depressants (e.g., barbiturates) or stimulants (e.g.,
or caffeine) of the central nervous system may alter the punished responding, but only in dosages
have a comparable influence on the food rewarded portion of the schedule.
The Geller-Seifter procedure is not the only method for screening drugs for their antianxiety
In fact, this method is so cumbersome and time consuming that its use tends to be limited to those
situations that require an especially rigorous test of a drug. Other tests which are, perhaps, not so
sensitive are much easier to use. For example, chlordiazepoxide will increase the amount of novel
that a rat will consume (Poschel, 1960; in Sepinwall
& Cook, 1978). This is apparently not related to
any changes in hunger per se, but rather to the more general response to novel (mildly aversive?)
situations. When a rat is exposed to a novel environment, there is an increase in plasma corticoid
levels. This index of stress can be effectively blocked with administration of minor tranquilizers
Lahti & Barshun, 1974).
Finally, a particularly easy method of measuring the response to punishment has been shown
consumption of salt solutions. Although rats show a positive taste response to a hypertonic
sodium chloride, the drinking of this solution is rather quickly limited by the aversive
consequences (the animal becomes thirsty as a result of drinking). The administration of minor
tranquilizers will increase the amount of hypertonic salt solution that is consumed (e.g., Falk &
Laboratory to Clinic and Back
Receptors for Phenothiazines
The pathway from the biochemist's laboratory to the clinician's administration of a drug is not
street. Although some of the screening tests may have face validity, there is always a danger that
aspect of the drug that causes an effect on a screening test is not always the same as the one that
its clinical effectiveness. This problem can never be eliminated completely, but the level of
can be raised when tight relationships emerge on the basis of extensive use of the drug in humans.
drug or class of drugs has been used extensively in the clinic, it may be possible to make a direct
comparison between the clinical results and some laboratory screening procedure. In the case of
tranquilizing drugs, there are two such relationships that are especially instructive.
As shown in Figure 4-11, there is a very strong relationship
the clinical dosage of the various
antipsychotic compounds and the ability of these compounds to replace another molecule
from dopamine receptors. The logic is as follows: If the dopamine receptors of a test object are
simultaneously exposed to haloperidol and some other compound, the two drugs will compete for
receptor sites. For the sake of illustration, if 100 molecules of a compound that has a strong
the dopamine receptor is pitted against haloperidol, perhaps as many as 80 of these molecules will
successful in occupying dopamine receptor sites. If a weak compound is used against haloperidol,
perhaps only 20 molecules would be successful. In order to get 80 molecules of the weak
into the receptor sites, a higher dosage (in this example, 400 molecules) would have to be used.
should be noted that this test is based on the D1 receptor for dopamine; see Chapter 8 for further
discussion of D1 and D2 receptors.)
In the clinic, the mechanism of action of the drug may not be known, and efficacy is based
relief of symptoms. Drugs that are weaker must be prescribed in larger amounts than drugs that
stronger. When a class of compounds has been given to thousands of patients and dosages have
adjusted, then the compounds can be ranked in terms of their relative strength, or
this does not necessarily mean that any one drug is better than another, but simply that some
more potent than others (the same relationship would hold if a single drug were "watered down"
a larger amount would have to be given to achieve an effective dosage). The observation of
depicted in figure 4-11 (after Creese et al,
1976). When the phenothiazines are rank ordered in
terms of their clinical potency, the list is virtually identical to that obtained when they are rank
terms of their affinity to the dopamine receptor. In other words, the potency of a drug to bind to
dopamine receptor is closely related to the potency of that drug to relieve psychotic symptoms in
clinic. It takes a hard nosed skeptic to believe that this would occur by chance.
In the case of the minor tranquilizers, a comparable relationship can be shown between the clinical potency of these compounds and their effectiveness in blocking the suppression of punished responses in the Geller-Seifter procedure. As schematized in figure 4-12, drugs that must be given in large quantities to produce the desired clinical effect must also be given in large quantities to change the behavior in the Geller-Seifter procedure.
The relationship of the benzodiazepines to neurotransmitter systems remained elusive for
These drugs do not significantly alter the brain concentrations of dopamine, norepinephrine or
although the turnover rate of all of these is reduced. Over the years, the compound known as GABA
(pronounced gabbuh; short for gamma amino butyric acid) has gained increasing respect as a
neurotransmitter. It is present in virtually every portion of the brain, it has consistently inhibitory
by virtue of opening chloride channels (cf., Chapter 8), and it is
the single most plentiful
neurotransmitter in the brain (see Olsen, 1987 for discussion). The
receptor for GABA has been
termed the GABA receptor complex (see Fig. 4-13) and is one of the most interesting developments
in neurochemistry. It would appear that there are three interacting receptors on this site: One of
is the primary GABA receptor, which regulates the Cl- channel. The second is a
responds to sedative and convulsant drugs. The third is receptive to benzodiazepines, and their
presence enhances the normal activity of GABA.
There is some possibility that the brain produces endogenous compounds that are comparable
benzodiazepines. The evidence for these naturally occurring substances is threefold: (a) labeled
diazepam is tightly bound to specific receptors, (b) the rank order of clinical potencies of the
benzodiazepines is highly correlated with the rank order of the ability of these compounds to
the labeled diazepine from these receptors (see Fig. 4-14; after Baestrup & Squires, 1978), and (c)
exposure to stress appears to block the binding of benzodiazepines, presumably because the sites
already have become occupied by some stress induced substance. Furthermore, the rank order of
clinical potencies is the same as the rank order of the ability of the compounds to displace this
compound from the receptor (cf., Moehler & Okada, 1977; see
Fig. 4-15; after Lippa et al, 1978).
There is a great deal of evidence that the brains systems that are involved with reacting to
and nonreward utilize acetylcholine as the neurotransmitter (cf., chapter 2 and Carlton, 1963, for
related discussion.) Both atropine and scopolamine (cholinergic blocking agents) alter the
rats in a variety of related situations: Behavior that is punished with shock persists. Behavior that
longer reinforced persists. Stimuli that signal a temporary period of nonreinforcement (time-out
experiments) are ignored. Schedules that require low rates of responding to obtain reward (drl
schedules) cannot be mastered. These results have been observed in different laboratories, using
different reinforcers and other testing parameters, and in different species. The conclusion that
cholinergic blocking agents reduce the response to punishment and nonreward is almost
These compounds have also been used in two other situations that seem even more relevant
reduction of stress responses. One of these has already been discussed: Atropine injections
the sudden death phenomenon in Richter's swimming task. The other involves the two way
procedure. Normal rats have great difficulty learning this task, presumably because a successful
avoidance response requires that the rat return to a location in which shock (or a signal for shock)
just been experienced. Scopolamine or atropine dramatically increase the ability to master this
presumably because it reduces the disabling response to conflict.
When this discussion was begun, it was asserted that these drugs influence the brain systems
control the responses to punishment and nonreward. The evidence for this assertion is strong, but
the same time provides a clue concerning the limited usage of these drugs in the clinic as stress
inhibitors. Perhaps the major reason why atropine and scopolamine are not suitable for routine
administration in humans is because they are too effective in the periphery. Recall
Laborit had used
scopolamine as a presurgical treatment prior to the development of chlorpromazine, it was
blocking the strong parasympathetic component of surgical shock. Likewise, this type of
blockade was effective in blocking the sudden death phenomenon in Richter's studies. However,
potency of these compounds in blocking the parasympathetic effector organs is itself a liability. In
case of diminishing surgical shock or preventing voodoo death, certain undesirable side effects
tolerated. But for routine administration, the accompanying dry mouth, dilated pupils, decreased
gastrointestinal activity and other autonomic effects are undesirable.
The progression of drugs that were used in the prevention of surgical shock provides a
good lesson of pharmacological principles. Scopolamine and atropine block the effects of
at the receptors of the actual target organs (i.e., the smooth muscles and glands) of the
system. In other words, the "command system" of the autonomic nervous system may remain
while the final response is blocked. Laborit went back one step and blocked the action at the
autonomic ganglia with low dosages of curare. This resulted in an autonomic stabilizing effect, by
reducing activity of both the sympathetic and parasympathetic divisions of the autonomic nervous
system. This type of action also had its limitations, because it was, in some sense, masking the
stages of a stress reaction that had already been initiated in the central nervous system. Laborit
seeking a drug effect that would block the initial stress interpretation in the brain, and
in chlorpromazine. The major point here is that it is preferable to forestall the stress reaction in its
stages than to allow it to develop and then block its effect at some later point along its synaptic
The problem with scopolamine and atropine is not that they lack central effects, but that they
central and peripheral blocking activities. In fact, there is strong evidence that the major influence
these compounds on the tasks outlined above is attributable to their effects upon the brain rather
the autonomic effectors. Both of these compounds are amines and in their normal states the
the side chain has three radicals attached to it and is neutral. These compounds can be
biochemically by adding a fourth radical (methyl) to the nitrogen leaving it with a positive charge.
resulting compounds (called quaternary amines) are commonly referred to as methyl atropine and
methyl scopolamine and have the very useful
being virtually unable to penetrate the blood
brain barrier (cf., Chapter 3.) This property means that nearly all of their blocking effects are
to the peripheral parasympathetic effectors, while brain acetylcholine systems are left to function
normally (see Figure 4-16).
A typical experimental design compares the behavior of a control group (saline injected) with
group injected with standard atropine and that of a group receiving methyl atropine. In virtually
experiment that has been done, the results are clear cut: Standard atropine reduces the response
punishment, nonreward and conflict, whereas methyl atropine (which has the same or even more
peripheral effects) has no effect on these behaviors. What this means is that the blockade of the
parasympathetic organs plays little or no role in the effects of these drugs on stress related
Virtually all of the effects can be attributed to their action on the brain. In this regard, it would be
interesting to know if methyl atropine would prevent the sudden, parasympathetic death in
swimming task (it probably would not) and if a form of scopolamine that worked only on the
not the periphery, would be a useful drug in the treatment of clinical stress disorders (it probably
would). In any event, we are not yet finished with the role of the autonomic nervous system in
responses, and we soon will see evidence that the peripheral responses are considerably more
important than they were once thought to be.
As in the more acute instances of shock reactions, the formation of ulcers can be blocked or
by the injection of cholinergic blocking drugs such as atropine. It is not, however, the treatment
choice in the clinic for the same reasons as discussed above, namely, side effects. It is one thing
demonstrate the effectiveness of atropine by blocking the formation of ulcers in an animal
that lasts a few hours or a few days. It is quite another to use such a broad spectrum drug over a
period of years in a human patient.
There are two pharmacological solutions to this problem that reflect importantly different
strategies. One of these, which we have seen above, is to counter the stress response at the
developmental stages in the brain. In this regard, the antianxiety compounds are successful in
experimental models and in the clinic. Chlorpromazine might also be effective, but because of its
potency is not routinely used for this purpose. Obviously, another even more desirable (and
approach is to eliminate the environmental conditions in the patient's life that lead to the formation
ulcers, but it is not always easy for the therapist to extricate people from their yoked control
The second pharmacological approach is to basically ignore the stressful situation per se and
specifically block the final stage of the stress response at the gastric receptors. As discussed
cholinergic blockade is not sufficiently specific, but there is an alternative. Once again, the roots
alternative go back to Laborit's work on surgical shock. He referred to the silent pain of the
knife, recognizing that the tissue damage resulted in a large autonomic response. This was due to
stimulating properties of histamine (literally meaning amine
tissues) on autonomic effectors.
Recall that Laborit's search for an autonomic stabilizer centered on antihistamines, but most of
compounds had broad actions in both the central and the peripheral nervous systems. Over the
the research that was spawned by these early problems led to the discovery of at least two types
histamine receptors, called H1 and H2 (see Douglas, 1980, for
Of these, the H1
receptors are far more common, being involved in response to injury, hypersensitivity reactions
(allergies), and other conditions. The H2 receptors are far less common, being primarily involved
the regulation of the volume and acidity of gastric secretion (see Figure
4-17). Thus, it is possible to
administer an H2 blocking compound that will block the hypersecretion of ulcer producing
acids, while leaving most of the remaining activities of histamine unaltered. One of these
cimetidine (trade name, Tagamet), has become one of the most
widely prescribed drugs in the world!
William James (1890) proposed an alternative view which, on the
surface, seems totally
unreasonable. The James-Lange formulation proposed that the emotion provoking stimulus
the autonomic nervous system directly (although there was a provision for central nervous system
involvement), but the actual experience of the emotion lagged behind and depended
of the autonomic reaction. Popular (and overly simplistic) metaphors of this theory proclaim that
individual "...is fearful because he is running from a bear", or "...is angry because she hit
This notion seems to have confused cause and effect.
Cannon (1927) pointed out a series of problems with James' view
the emotional experience: (a)
The visceral response is slow to develop. (b) The viscera themselves are rather insensitive, even
physical trauma such as cutting or cauterization. (c) The same response (e.g., an elevated heart
can be elicited by fear, running around the block, or falling in love. (d) Patients with spinal
lead to paralysis and loss of bodily sensations experience full emotions. (e) Injections of
not result in emotional experiences. At the time of this argument, Cannon was perhaps the
physiologist of the world, and William James was merely a gifted writer, philosopher, and
who was treading on the foreign soil of physiology. Cannon's view prevailed.
Cannon's professional stature overshadowed some of the weaknesses of his objections.
weaknesses became more and more apparent as additional information about the autonomic
system unfolded through the years. It is true that visceral changes are sluggish and slow to
so is it true that the full emotional experience is often slow to develop. An all-too-frequent
is the near miss of an automobile accident which almost instantly mobilizes complicated motor
responses, while the full range and impact of the emotions may come seconds, minutes, or even
later. It is also true that the viscera can be cut, cauterized and otherwise insulted during surgery
little or no sensation to the patient, but this is a moot point. We certainly can experience the rapid
heartbeat, flushed skin, and butterflies in the stomach during emotional experiences. Cannon's
about the origins of an increased heart rate was also weak, in that he failed to recognize the
that different emotions engender different patterns of autonomic responses (cf., Ax, 1953; Ekman, et
al, 1983; Funkenstein, 1955). Patients who lack the ability to
to feel somesthetic stimulation
of the body still retain a large portion of autonomic sensitivity via the cranial nerves, especially the
nerve. These patients also report a lack of emotional intensity, feeling "as if" they were angry.
the experiments involving the effects of adrenaline injections were incomplete in design, missing
important point that even James missed. These studies form the basis for the remainder of this
The experiments of Schachter, Singer and their colleagues (e.g., Schachter,
1971; Schachter &
Singer, 1962) have shed new light on the James-Lange theory of emotions. Their results
that autonomic arousal can set the stage for (rather than being the result of) emotional experience,
elucidate some of the difficulties that other experimenters (including Cannon and James) have had
triggering emotional reactions with adrenalin injections. We turn now to a consideration of some
A typical experimental procedure employed by Schachter and Singer involves the injections of
adrenaline or saline (a placebo) and the presence or absence of an emotion provoking situation.
each study, the subjects who had received the injections were divided into two groups. One
simply filled out a questionnaire that contained some rather pointed items. The second group
the same questionnaire, but a confederate who pretended to be a subject vividly expressed his
at the nature of the questions, tore up the response sheet, and stomped out of the room. Post-test
interviews showed the following pattern of results: (a) The questionnaire per se did not elicit
either the subjects injected with the placebo or those injected with adrenalin. (b) The subjects
with the placebo did not experience anger, even when exposed to the confederate. (c) The
who had received adrenalin injections, however, were strongly influenced by the confederate and
experienced anger over the nature of the questionnaire.
The interpretation of these results is that the emotional experience requires both autonomic
a relevant cognition about the environment. Extending this notion further, it was proposed that
subjects explained their autonomic arousal by attributing it to the anger about the questionnaire,
expressed by the confederate. Since the questionnaire alone was a rather mild stimulus, it could
provide a sufficient account for the autonomic arousal until the flame was fanned, so to speak, by
The explanation outlined above would be very tenuous, were it not for the complementary
additional experiments. One such experiment used exactly the same treatments (adrenaline or
and the subjects were asked to fill out a long and tedious questionnaire. This time, the
rebelled against the tedium of the task and began a high spirited game of basketball, using the
wastebasket and some extra copies of the questionnaire. The pattern of results was the same:
was no particular emotion attached to the questionnaire per se for either the placebo or the
groups. Likewise, those subjects who had received the placebo paid little attention to the
However, those subjects whose sympathetic nervous systems had been aroused by the adrenaline
strongly influenced by the antics of the confederate as revealed by their post-test expressions of
There is a great deal of power in these two experiments. A particular emotion cannot be
the effects of a drug, the adrenaline. Nor can an emotional experience be triggered by the mere
presence of a mild environmental situation. But the combination of sympathetic arousal and an
appropriate environmental situation can produce a full blown emotional reaction. In the words of
Schachter and Singer, the subjects who have been injected with adrenaline have a state of arousal
is in search of an appropriate cognition. These results have been extended in a number of novel
designs, including one in which prior adrenaline injections increased the number of belly laughs
slapstick comedy film. The framework of this theory has even included a naturalistic setting in
male subjects who had just walked across a high suspension bridge (presumably providing their
adrenaline) rated a female confederate significantly more attractive than males who had not
A final experimental manipulation provided the capstone for this notion of emotional
subjects were informed that the drug that they had received was adrenaline and told that it would
produce an increase in heart rate, some flushing of the skin, and a general feeling of arousal, the
emotional experience was forestalled: The symptoms were attributed to the drug action rather
the antics of the confederate or the humor of the comedy.
The results of these experiments add a new dimension to the effects of various drugs,
that are designed to stabilize emotions or reduce anxiety. It is clear that the effects of these drugs
be either on the central interpretation of the environment (i.e., the cognition) or on the peripheral
aspects. It is very likely that the autonomic stabilizing effects play an important role in changing
individual's interpretation of the environment. Just as the subjects in Schachter's experiment say,
essence, that they must be experiencing an emotion because that is the only explanation they have
their state of arousal, so is it possible that an individual whose autonomic nervous system has been
stabilized by an antianxiety agent may conclude that the situation must not be anxiety provoking
there is no autonomic arousal. Figure 4-16 shows a summary of some of these effects.
2. Pavlovian conditioning procedures show that fear can be evoked by previously neutral
have been paired with aversive events.
3. Instrumental conditioning involves two factors: Pavlovian conditioning of fear responses
of behaviors that are instrumental in changing these relationships.
4. The major response to short term stressors is the so-called flight or fight response of the
5. Longer exposures to stressors can result in the progressively more severe stages of the
6. Acute trauma such as surgery can lead to the shock syndrome, a diffuse outpouring of the
autonomic nervous system.
7. The lack of a coping response for acute, profound stressors can lead to sudden death
overreaction of the parasympathetic nervous system.
8. The response to stress can be systematically changed by behavioral and pharmacological
9. The major forces that lead to ulcers are the inability to predict or control aversive events,
presence of conflicting consequences (sometimes rewarded; sometimes punished) of behavior.
10. The stress response is more closely related to the interpretation of the environment than
physical intensity of the aversive stimuli.
11. The search for better stabilizers of the autonomic nervous system led to the discovery of
chlorpromazine and related phenothiazines known, collectively, as tranquilizers or antipsychotic
12. The benzodiazepines rather specifically reduce the effects of punishment, and are widely
prescribed (e.g., Librium and Valium) as antianxiety drugs.
13. The phenothiazines have a high affinity for dopamine receptors.
14. The benzodiazepines have a high affinity for specific receptors that have not been linked
GABA receptor complex. The presence of these receptors has suggested the possibility of an
endogenous antianxiety compound in the brain.
15. Anticholinergic drugs appear to have excellent anti-punishment properties in animal
but because of the peripheral side effects, they have little clinical value in the treatment of day to
16. The quaternary forms of atropine and scopolamine have been useful experimentally
block cholinergic synapses in the periphery, but do not cross the blood brain barrier.
17. Cimetidine (Tagamet) is a very specific blocker of the H2 histamine receptor, and is
prescribed to reduce the gastric acid secretion that can lead to ulcers.
18. Feedback from the autonomic nervous system plays an important role in determining
not an emotion will be experienced; environmental cues interact with this feedback to determine
nature of the emotional response.
Blood brain barrier
General Adaptation Syndrome
Long delay conditioning
Stage of exhaustion
Stage of resistance
Two way avoidance
Two factor theory