Index of Figures
Chapter 1 (Go to beginning of figure index)
- Figure 1 - 1: Sherrington's experiments on the
electrophysiology of the synapse
- Schematic summary of Sherrington's experiments on the electrophysiology of the synapse.
- Figure 1 - 2: Loewi's demonstration of chemical
- Otto Loewi's experiment demonstrating the chemical transmission of nerve impulses.
- Figure 1 - 3: Bernard's experiments on the nerve-muscle
- Claude Bernard's experiments demonstrating that curare acts at the junction between the
nerve and the muscle.
- Figure 1 - 4: The source of energy for electrical activity of
the nervous system
- The separation of charged particles produces a resting potential across the membrane of the
- Figure 1 - 5: Propagation of the action potential
- The action potential sets up the stimulus for the continued propagation of the potential,
which appears as a wave of electrical activity that travels down the axon.
- Figure 1 - 6: Release of neurotransmitter
- The arrival of the action potential causes the release of chemical messengers from the
terminal endings of the axon.
- Figure 1 - 7: Steps in the process of chemical transmission
at the synapse
- Major steps in the process of chemical transmission.
- Figure 1 - 8: Chemical bases of dual control by the
autonomic nervous system
- Pupillary responses to two different chemical inputs cause contrasting responses to
autonomic smooth muscles.
- Figure 1 - 9: Dual control by the autonomic nervous
- The autonomic nervous system uses a combination of different anatomical organizations and
different chemical mediators to cause different (usually opposing) effects in the same target
- Figure 1 - 10: Receptor sites determine response to
- The autonomic control of the urinary bladder exemplifies both the opposing interactions of
the sympathetic and parasympathetic system and the differing effects that the same compound can
have on different sets of smooth muscles.
- Figure 1 - 11: Multiple receptor sites for a
- Schematic summary of some transmitter-receptor possibilities.
- Figure 1 - 12: Chemical organization of the autonomic
- Outline of different receptor types and chemical transmitters in the autonomic nervous
- Figure 1 - 13: Chemical specificity of the
- More specific changes in behavior are produced by chemical stimulation than by lesions of
- Figure 1 - 14: The interactions of brain, behavior and
- The brain, behavior, and the environment have interpenetrating effects.
Chapter 2 (Go to beginning of figure
- Figure 2 - 1: Subtractive logic as it applies to lesion and
- Subtractive logic as it applies to lesion and pharmacological experiments.
- Figure 2 - 2: Subtractive logic as it applies to the famous
case of Phinnaeus P. Gage
- Subtractive logic as it applies to the famous case of Phinnaeus P. Gage.
- Figure 2 - 3: Subtractive logic as it applies to the metabolic
disorder of phenylketonuria (PKU)
- Subtractive logic as it applies to the metabolic disorder of phenylketonuria (PKU).
- Figure 2 - 4: Encephalization of the developing
- Schematic representation of the structural development of the brain.
- Figure 2 - 5: Life span of a cholinergic neuron
- Schematic representation of the life span development of a cholinergic neuron.
Chapter 3 (Go to beginning of figure
- Figure 3 - 1: Drug molecules pass through the cell
- Basic elements of the cell membrane determine access of drugs to body tissues.
- Figure 3 - 2: The dose-response curve
- Dose-response curve shows that behavior changes as drug levels in the plasma change.
- Figure 3 - 3: Time course of drug effects
- Following a single dose of a drug, the concentration of drug in the plasma increases to a
peak, and then declines. Behavioral changes coincide with this changing drug concentration.
- Figure 3 - 4: Behavioral effects of repeated doses of
- Repeated doses of a drug maintain the drug in the system, but the plasma concentrations
cycle above and below the average level. Behavioral changes follow these fluctuations in plasma
concentration of the drug.
- Figure 3 - 5: Effects of a drug depend upon initial rates of
- The law of initial values refers to the different drug effects that are seen when the initial rates
of behavior are different.
- Figure 3 - 6: Effects and side effects of drugs
- A variety of different effects can be seen with increases in the plasma concentration of a
drug. In some cases, these differences in effect might be desirable (e.g., effect A and effect B).
Along with these, some combination of undesirable effects (side effects C, D and E) might also
- Figure 3 - 7:
Effects of epinephrine and acetylcholine on blood pressure
- Epinephrine and acetylcholine each produces dose-related changes in blood pressure, but by
Low doses of epinephrine act on beta receptors and decrease blood pressure by
High doses of epinephrine act on alpha receptors and increase blood pressure by
Low doses of acetylcholine act on muscarinic receptors and decrease blood pressure by
High doses of acetylcholine act on the nicotinic receptors of the autonomic ganglia and
increase blood pressure indirectly through activation of the sympathetic nervous system.
- Figure 3 - 8: The blood-brain barrier
- The blood-brain barrier protects the brains from certain classes of compounds while allowing
other classes of compounds to have free access.
- Figure 3 - 9: Summary of the effects of drugs on
- Summary of the major biochemical effects that drugs may have at the synapse:
1. Precursor compounds
2. Synthesis blockade
3. Transmitter depletion
4. Prevention of release
5. Receptor inhibition
7. Inactivation blockade
8. Reuptake blockade
9. False transmitters (+)
10. False transmitters (-)
11. Conduction blockade
- Figure 3 - 10: The interrelationships of molecular structure,
biochemical activity and behavioral effect
- The interrelationships of the drug classifications that are based on drug effects, drug actions,
and drug structures:
A. Consistent relationships suggest biochemical substrates for particular behaviors.
B. Consistent structure-activity relationships suggest chemical structures for synthesis of related
C. Consistent relationship suggests that the drugs within a particular class may share a common
Chapter 4 (Go to beginning of figure
- Figure 4 - 1:
Pavlovian fear conditioning
- Three types of Pavlovian conditioning procedures for modeling of fear:
Delay conditioning. Conditioned responses, including fear, begin to occur during the CS
presentation before the US is presented.
Long-delay conditioning. Conditioned fear responses move forward in time during long
CS presentations and, with continued training, reach maximal levels during the interval
just preceding the presentation of the aversive US.
Trace conditioning. Conditioned fear can be observed during the interval when only the
trace, or memory, of the CS is present.
- Figure 4 - 2:
Shuttle box instrumental fear conditioning
- The shuttle box is one of the standard pieces of apparatus for studying learned responses to
One-way escape conditioning is very simple, requiring only that the subject move to the
other end of the chamber to escape the ongoing electric shock.
One-way avoidance conditioning adds an explicit warning signal (CS) that shock will
begin shortly, providing an opportunity to move to the safety zone and avoid the electric
Two-way avoidance provides a CS at either end to allow the avoidance of electric shock,
but the conflict of returning to a place that is not always safe sets up conflict and makes
the task difficult to learn.
- Figure 4 - 3: Sympathetic nervous system response to
- The sympathetic and adrenal responses facilitate coping with acute episodes of stress.
- Figure 4 - 4: Parasympathetic nervous system response to
- The parasympathetic system predominates when acute episodes of stress provide no obvious
coping response. Under non-stressful conditions, each of the effector organs responds
individually as necessary.
- Figure 4 - 5: Richter's experiments on the emotional causes
of stress syndrome
- Richter's experiments demonstrated the importance of both the behavioral interpretation of
"hopeless" stressors and the activity of the parasympathetic division of the autonomic nervous
- Figure 4 - 6: The triad design for studying the importance
of prediction and control
- The triad design has been useful in determining the importance of prediction and control of
aversive events and the susceptibility to ulcer formation.
- Figure 4 - 7: Stomach ulcers under conditions of
prediction, control and conflict
- The relative incidence of ulcer formation under various conditions of prediction, control, and
- Figure 4 - 8: Curare as an autonomic nervous system
- Curare was used to block the autonomic ganglia of both divisions of the autonomic nervous
- Figure 4 - 9: Impact of the discovery of
- The discovery of chlorpromazine produced a dramatic decrease in the number of
schizophrenia patients who required chronic hospitalization. The curves in the upper panel are
based on a one-percent incidence of schizophrenia in the general population, with one-third of
these requiring chronic hospitalization before the advent of phenothiazines. Current costs of
schizophrenia to society have been estimated at two percent of the gross national product (GNP).
Projected values and values prior to 1955 in the lower panel of the figure are based on costs that
are four times that value.
- Figure 4 - 10: Effects of antianxiety drugs on punished
- Antianxiety drugs block the suppressant effects of punishment in the Geller-Seifter
procedure without changing the rate of food-rewarded responding. (Slash marks on graph
- Figure 4 - 11: Clinical effectiveness of antipsychotic drugs
related to effects on dopamine receptors
- Antipsychotic drugs that are most effective in the clinic are also most effective in displacing
haloperidol from dopamine receptors.
- Figure 4 - 12: Clinical effectiveness of antianxiety drugs
related to effects on punished responding
- Antianxiety drugs that are most effective in the clinic are also most effective in blocking the
suppressant effects of punishment in the Geller-Seifter procedure.
- Figure 4 - 13: The GABA receptor complex
- The benzodiazepines appear to act on receptors that modulate the activity of GABA in the
GABA receptor complex.
- Figure 4 - 14: Clinical effectiveness of antianxiety drugs
related to effects on GABA receptor
- Antianxiety drugs that are most effective in the clinic are also most effective in displacing
labeled diazepam from GABA receptors.
- Figure 4 - 15: Evidence for an endogenous antianxiety
- Antianxiety drugs bind to receptors that may be specific for some (as yet unidentified)
endogenous antianxiety substance.
- Figure 4 - 16: Evidence that anticholinergic antianxiety
drugs act on the brain
- The quaternary forms of atropine and scopolamine block the cholinergic synapses of the
periphery but do not cross the blood-brain barrier. The anti-punishment effects of these drugs
require action on brain neurons.
- Figure 4 - 17: Histamine (H2) blockers decrease stomach
- Cimetidine (Tagamet) specifically blocks H2 receptors while the other histamine receptors
continue to function normally.
Chapter 5 (Go to beginning of figure
- Figure 5 - 1: Distinguishing between the reflexive and
emotional components of pain
- The flinch-jump procedure can distinguish between the reflexive and emotional components
of the response to pain.
- Figure 5 - 2: Measuring pain thresholds
- The paw-lick and tail-flick tests measure the threshold of pain produced by mild heat stimuli.
- Figure 5 - 3: Receptor binding technique
- Radioactive substances that have a specific affinity to brain receptors (receptor binding) can
be isolated along with the receptor membrane.
- Figure 5 - 4: Clinical effectiveness of opiate agonists and
antagonists related to effects on opiate receptors
- The clinical potency of opiate drugs is related to their affinity for binding to brain opiate
receptors. This relationship holds for both opiate agonists and opiate antagonists.
- Figure 5 - 5: Beta-lipotropin as source of stress-response
- The beta-lipotropin molecule contains several of the same sequences of amino acids that
comprise peptides that are known to be important in the stress response.
- Figure 5 - 6: Neurochemical systems in pain
- Schematic summary of the neural and hormonal systems that mediate pain and pain
- Figure 5 - 7: Pain produces analgesia
- The type of analgesia that is produced is related to the impact of the aversive stimulus.
- Figure 5 - 8: Interpretation of painful event determines
- The triad design shows that the interpretation of the painful stimulus determines whether or
not analgesia will ensue.
- Figure 5 - 9: Effects of naloxone on analgesia induced by
- Analgesia can be produced by the experience of social defeat in mice.
- Figure 5 - 10: Cross-tolerance between social defeat and
- Cross-tolerance exists between the effects of morphine and social defeat.
- Figure 5 - 11: The effects of either morphine, placebo
drugs, or acupuncture on dental pain can be blocked by an opiate blocker
- The effects of either morphine, placebo drugs, or acupuncture on dental pain can be blocked
by an opiate blocker.
- Figure 5 - 12: Cellular and humoral immunological
- Schematic diagram of the two major types of immunological responses.
- Figure 5 - 13: Humoral response of the immune
- The B-lymphocytes mediate the humoral response of the immune system.
- Figure 5 - 14: Cellular response of the immune
- The cellular response of the immune system involves the proliferation of T-cells.
- Figure 5 - 15: Influence of genetics and early environment
on milk allergies
- The incidence of allergic reactions to milk is related to both the genetic history and infant
feeding styles of the individual.
- Figure 5 - 16: Effects of inescapable shock on immune
- Inescapable shock suppresses the proliferation of T-cells.
- Figure 5 - 17: Experimental allergic myasthenia
- Experimental allergic myasthenia gravis can be produced by antibodies to foreign nicotinic
- Figure 5 - 18: Experimental "allergic" diabetes
- A model for an immunological response that interferes with receptors.
- Figure 5 - 19: Limbic system mediation of the
hypothalamic stress response
- A summary model of the general features of the hypothalamic and pituitary contributions to
different forms of stress reactions.
Chapter 6 (Go to beginning of figure
- Figure 6 - 1: Generalized learned
- The learned helplessness that results from exposure to the absence of control generalizes to
- Figure 6 - 2: Catecholamine degradation enzymes
- Catecholamines that are not protected within compartments of the terminals are metabolized
by MAO. Free-floating catecholamines in the synaptic zone outside the cell are metabolized by
- Figure 6 - 3: Depletion and repletion of catecholamines
- The depletion and repletion of transmitter stores has linked the catecholamines to reward.
- Figure 6 - 4: Medial forebrain bundle (MFB)
- Noradrenergic fibers arising from the locus coeruleus and dopaminergic fibers arising from
the ventral tegmental area converge in the MFB reward system.
- Figure 6 - 5: The brain-behavior-environment
- Manipulations of brain chemistry or anatomy change the response to rewards. The
remainder of this chapter will show how behavior and the environment can change the brain
systems that are responsible for mediating reward.
- Figure 6 - 6: Swim test of learned helplessness
- Rats that have been exposed to uncontrollable electric shocks engage in fewer coping
responses in the modified swim test.
- Figure 6 - 7: Stress affects tyrosine hydroxylase
- Exposure to uncontrollable shock produces a temporary decrease in the production of
norepinephrine. Repeated exposure to mild, controllable stress increases the activity of this
- Figure 6 - 8: Role of alpha-2 autoreceptors in
- Autoreceptors in the locus coeruleus regulate transmitter release in the anterior cortex.
- Figure 6 - 9: Effects of amphetamine and cocaine on
- Amphetamine displaces dopamine from vesicles. Cocaine blocks dopamine reuptake. Both
effects increase the activity of the synapse.
- Figure 6 - 10: Role of MAO in depression
- The effects of MAO inhibitors in the reserpine model of depression.
- Figure 6 - 11: Specificity of MAO inhibitors
- The ability to specifically block the MAO-B isoenzyme may result in fewer side effects in the
treatment of depression. Nonspecific MAO blockers also influence MAO-A in the periphery,
leading to increases in norepinephrine. Then, dietary tyramine (from wine, cheese, etc.) can
indirectly release the NE, causing dangerous side effects such as increased blood pressure.
- Figure 6 - 12: Effects of tricyclic antidepressants on
- The tricyclic drugs avoid the "wine and cheese" problem, but still have potentially dangerous
interactions with other drugs.
- Figure 6 - 13: Metabolites of norepinephrine
- Abnormalities in the metabolic pathways of catecholamines may provide information for
better diagnosis and treatment of depression. The numerous alternatives for pathways of
degradation of NE can alter the amounts of DHPG, MHPG, and VMA that are produced. These
biochemical markers may help to predict which drugs will be effective.
- Figure 6 - 14: Antidepressant drugs affect
- The long delay of the therapeutic effects of antidepressant drugs suggests that the drugs may
trigger neuromodulatory changes.
- Figure 6 - 15: Lithium controls mania
- Lithium appears to control bipolar depression by eliminating the manic phase of the disorder.
- Figure 6 - 16: Exposure to stress increases vulnerability to
- A single exposure to the lack of control makes the subjects more vulnerable to the effects of
similar stressors that occur shortly thereafter.
- Figure 6 - 17: Behavioral reward increases norepinephrine
- The attainment of rewards produces neurochemical changes in the brain, enhancing the
synthesis and release of NE.
Chapter 7 (Go to beginning of figure
- Figure 7 - 1: Genetics of schizophrenia
- Close relatives of schizophrenic patients are much more likely to develop the disorder.
- Figure 7 - 2: Neurotoxic effects of 6-hydroxy dopamine
- The administration of 6-hydroxy dopamine (6-OHDA) to rats blocks the lever-pressing for
rewarding brain stimulation and produces the waxy flexibility that characterizes some forms of
- Figure 7 - 3: Catecholamine synthesis
- Synthetic pathways of the catecholamines.
- Figure 7 - 4: Blockade of tyrosine hydroxylase reduces NE
- Tyrosine hydroxylase is shown to be the rate-limiting enzyme by blocking experiments: Only
the blockade of tyrosine hydroxylase produces a direct reduction of NE synthesis.
- Figure 7 - 5: The dopamine beta hydroxylase (DBH) model
- The DBH model proposes a shift in the location of the rate-limiting enzyme in catecholamine
synthesis (compare to Fig. 7-3).
- Figure 7 - 6: The clinical potency of antipsychotic drugs is
related to ability to block D2 receptors
- Phenothiazines that are most effective in treating schizophrenia are also most effective in
blocking the D2 (but not the D1) receptors for dopamine.
- Figure 7 - 7: Dual effects of dopamine receptors
- The D1 receptors facilitate adenyl cyclase, whereas the D2 receptors inhibit this second
messenger. These processes change the protein-synthesizing capabilities of the cell.
- Figure 7 - 8: Effects of endorphins on dopamine
- Endorphins can influence the release of dopamine or alter the number or sensitivity of
- Figure 7 - 9: Multiple transmitters and receptors regulate
neuron's response to stimulation
- The most recent models of the synapse suggest the presence of multiple transmitter
substances that may be stored within different vesicles. In the example shown, low levels of
stimulation involve only the primary neurotransmitter. Intermediate levels of stimulation also
involve the blocking of inhibitory autoreceptors. Strong stimulation releases this inhibition and
allows maximal postsynaptic stimulation.
- Figure 7 - 10: Neuromodulatory effects of phenothiazines
- The dynamic regulation of the synapse has led to a neuromodulatory model of the action of
phenothiazines in schizophrenia.
- Figure 7 - 11: Dopaminergic pathways in the
- Dopaminergic pathways that serve the extrapyramidal motor system arise from the
substantia nigra; those that serve the limbic system arise from the ventral tegmental area. The
latter are presumably those involved with schizophrenia.
Chapter 8 (Go to beginning of figure
- Figure 8 - 1: The ascending reticular activating system
- The ascending reticular activating system (ARAS) controls the level of arousal.
- Figure 8 - 2: Active sleep and arousal centers in the brain
- The location of active centers for sleep and arousal have been shown by the effects of three
- Figure 8 - 3: EEG changes in sleep
- Stylized examples of the relationship between the EEG and levels of arousal.
- Figure 8 - 4: Neurotransmitters of sleep and arousal
- The major neurotransmitters of sleep (5-HT) and of arousal (NE, DA, and ACh).
- Figure 8 - 5: Brain circuitry of circadian rhythms
- Brain circuitry involved with the maintenance of circadian rhythms.
- Figure 8 - 6: Barbiturate effects depend on circadian
- The dosage of barbiturate required to reach the anesthetic level varies as a function of
- Figure 8 - 7: Interaction of Yerkes-Dodson Law with task
- The inverted U-shapes relationship between arousal and performance, known as the Yerkes-Dodson law, interacts with the complexity of the task.
- Figure 8 - 8: Interactions among arousal, behavior, and
- The interactive effects of arousal, behavior, and the environment. Drugs that influence these
interactions have powerful effects on behavior.
- Figure 8 - 9: Effects of strychnine and tetanus toxin on
- Strychnine blocks the receptors of inhibitory circuits within the spinal reflex systems.
Tetanus toxin blocks the release of the inhibitory transmitter.
- Figure 8 - 10: Effects of picrotoxin on GABA receptors
- Picrotoxin acts on the GABA receptor complex to reduce the effects of GABA.
- Figure 8 - 11: Effects of pentylenetetrazol on action
potential recovery time
- Pentylenetetrazol reduces the recovery time between consecutive action potential.
- Figure 8 - 12: Effects of xanthine derivatives on Ca++
- Xanthine derivative (caffeine, theophylline, and theobromine) increase Ca++ permeability.
Ca++ plays an essential role in many aspects of cell membrane excitation. Xanthine derivatives
facilitate Ca++ entry and increase levels of excitation.
- Figure 8 - 13: Effects of nicotine on acetylcholine
- Nicotine mimics acetylcholine at the autonomic ganglia but can block function by producing
- Figure 8 - 14: Effects of amphetamine on catecholamine
- Amphetamines cause indirect stimulation by releasing newly synthesized catecholamines
- Figure 8 - 15: Effects of cocaine on catecholamine
- Cocaine cause indirect stimulation by blocking the reuptake of catecholamines (especially
dopamine). The local anesthetic effects are caused by blocking Na+ permeability.
- Figure 8 - 16: Effects of barbiturates and benzodiazepines
on GABA receptors
- Barbiturates and benzodiazepines enhance the effects of inhibitory GABA neurons via two
different receptors on the GABA receptor complex.
- Figure 8 - 17: Behavioral symptoms of alcohol ingestion
- Increases in the amount of alcohol consumption cause a progressive loss of sensory and
motor capabilities. Large amounts can cause coma and death.
- Figure 8 - 18: Anticholinergic effects on the
- Atropine and scopolamine block ACh receptors and interfere with septohippocampal theta
Chapter 9 (Go to beginning of figure
- Figure 9 - 1: Physiological mechanisms of tolerance
- Physiological mechanisms of tolerance that reduce the contact of the drug with the
- Figure 9 - 2: Compensatory responses to drug effects
- Some compensatory responses to drug effects. Both excitatory and inhibitory systems may
change (in response to the presence of a drug) to return function to normal.
- Figure 9 - 3: Mechanism of tachyphylaxis
- Ephedrine effects as a model of tachyphylaxis. (b.p. = blood pressure; D1 to D6 refer to
- Figure 9 - 4: Tolerance due to reduction of receptors
- Reduction of receptors through neuromodulation results in tolerance to the high levels of
acetylcholine that are maintained during inhibition of acetylcholinesterase (AChE).
- Figure 9 - 5: Enzyme induction speeds drug metabolism
- Enzymes induction provides a way to increase the speed of drug metabolism.
- Figure 9 - 6: Development of barbiturate tolerance
- Barbiturate effects before and after the development of tolerance.
- Figure 9 - 7: Drug withdrawal produces rebound effects
- Continued exposure to a drug can sometimes trigger compensatory responses that
effectively counteract the drug effects. Under these conditions, the response to the absence of the
drug can be greater than the response to the drug itself.
- Figure 9 - 8: Behavioral tolerance
- The pre-post design has been useful in demonstrating behavior tolerance. The shaded areas
indicate the amount of some behavior that is being tested.
- Figure 9 - 9: Affective withdrawal produces rebound
- Opponent-process theory of emotion suggests naturally occurring rebound effects.
- Figure 9 - 10: Opponent-Process model of addiction
- The opponent-process model of the development and maintenance of heroin addiction.
- Figure 9 - 11: Drugs as reinforcers
- Rats and other laboratory animals can demonstrate abuse potential of drugs through the self-administration procedure.
- Figure 9 - 12: Drug effects depend on expectations
- Real or false information about alcohol can change the behavioral effect. This is the so-called
think-drink effect described by Carpenter.