Psychopharmacology Drugs, the Brain, and Behavior

by Meyer, Jerrold S.; Quenzer, Linda F.

• ISBN13: 9780878935345
• ISBN10: 0878935347
• Format: Hardcover
• Copyright: 2004-10-18
• Publisher: Sinauer Associates is an imprint of Oxford University Press

Summary

Univ. of Massachusetts, Amherst. Textbook discusses how drugs and other substances affect cognitive performance and behavior. Topics include principles of pharmacology, drug abuse, dependence, addiction, opiates, alcohol, nicotine, caffeine, marijuana, hallucinogens, and more. Features full-color and halftone images, and graphs.

Table of Contents

Preface	xvi
Principles of Pharmacology	3	(30)
Pharmacology: The Science of Drug Action	4	(3)
Pharmacokinetic Factors Determining Drug Action	7	(14)
Methods of drug administration influence the onset of drug action	7	(4)
Multiple factors modify drug absorption	11	(2)
Drug distribution is limited by selective barriers	13	(3)
Depot binding alters the magnitude and duration of drug action	16	(1)
Biotransformation and elimination of drugs contributes to bioavailability	17	(4)
Pharmacodynamics: Drug--Receptor Interactions	21	(6)
Extracellular and intracellular receptors have several common features	21	(3)
Dose--response curves describe receptor activity	24	(1)
The therapeutic index calculates drug safety	25	(1)
Receptor antagonists compete with agonists for binding sites	25	(2)
Biobehavioral Effects of Chronic Drug Use	27
Repeated drug exposure can cause tolerance	27	(3)
Chronic drug use can cause sensitization	30
Herbal Medicine---Panacea or Hazard?	5	(3)
Naming Drugs	8	(14)
Drug Categories	22	(11)
Structure and Function of the Nervous System	33	(30)
Cells of the Nervous System	34	(6)
Neurons have three major external features	34	(3)
Characteristics of the cell membrane are critical for neuron function	37	(2)
Glial cells provide vital support for neurons	39	(1)
Electrical Transmission within a Neuron	40	(7)
Ion distribution is responsible for the cell's resting potential	40	(2)
Local potentials are small, transient changes in membrane potential	42	(1)
Sufficient depolarization at the axon hillock opens voltage-gated Na+ channels, producing an action potential	43	(1)
Drugs and poisons alter axon conduction	44	(3)
Organization of the Nervous System	47
The nervous system comprises the central and peripheral divisions	48	(5)
CNS functioning is dependent on structural features	53	(1)
The CNS has six distinct regions reflecting embryological development	54	(4)
The cerebral cortex is divided into four lobes, each having primary, secondary, and tertiary areas	58
Epilepsy	46	(3)
Finding Your Way in the Nervous System	49	(14)
Chemical Signaling by Neurotransmitters and Hormones	63	(26)
Chemical Signaling between Nerve Cells	64	(1)
Neurotransmitter Synthesis, Release, and Inactivation	65	(7)
Neurotransmitters encompass several different kinds of chemical substances	65	(1)
Classical transmitters and neuropeptides are synthesized by different mechanisms	66	(1)
Chemicals that don't act like typical neurotransmitters are sometimes called neuromodulators	67	(1)
Neurotransmitter release involves the exocytosis and recycling of synaptic vesicles	67	(3)
Several mechanisms control the rate of neurotransmitter release by nerve cells	70	(1)
Neurotransmitters are inactivated by reuptake and by enzymatic breakdown	71	(1)
Neurotransmitter Receptors and Second-Messenger Systems	72	(6)
There are two major families of neurotransmitter receptors	72	(3)
Second messengers work by activating specific protein kinases in a cell	75	(1)
Tyrosine kinase receptors mediate the effects of neurotrophic factors	76	(2)
Pharmacology of Synaptic Transmission	78	(2)
The Endocrine System	80
Endocrine glands can secrete multiple hormones	81	(3)
Mechanisms of hormone action vary	84	(1)
Why is the endocrine system important to pharmacologists?	84
Just Say No	77	(8)
Stress, Glucocorticoids, and Psychostimulants	85	(4)
Methods of Research in Neurobehavioral Pharmacology	89	(30)
Techniques in Neuropharmacology	90	(1)
Multiple Neurobiological Techniques for Assessing the CNS	90	(15)
Stereotaxic surgery is needed for accurate in vivo measures of brain function	90	(5)
Neurotransmitters, receptors, and other proteins can be quantified and visually located in the CNS	95	(5)
New tools are used for imaging the structure and function of the brain	100	(4)
Genetic engineering helps neuroscientists to ask and answer new questions	104	(1)
Techniques in Behavioral Pharmacology	105	(1)
Evaluating Animal Behavior	105	(1)
Animal testing needs to be valid and reliable to produce useful information	107	(1)
A wide variety of behaviors are evaluated by psychopharmacologists	108	(5)
Operant conditioning techniques provide a sensitive measure of drug effects	113
Using the Techniques of Neuropsycho-pharmacology	106	(3)
Drug Development and Testing	109	(10)
Catecholamines	119	(20)
Catecholamine Synthesis, Release, and Inactivation	120	(4)
Tyrosine hydroxylase catalyzes the rate-limiting step in catecholamine synthesis	120	(1)
Catecholamines are stored in and released from synaptic vesicles	121	(2)
Catecholamine inactivation occurs through a combination of reuptake and metabolism	123	(1)
Organization and Function of the Dopaminergic System	124	(8)
Two important dopaminergic cell groups are found in the midbrain	124	(4)
There are five main subtypes of dopamine receptors organized into D1- and D2-like families	128	(1)
Dopamine receptor agonists and antagonists affect locomotor activity and other behavioral functions	129	(3)
Organization and Function of the Noradrenergic System	132
The ascending noradrenergic system originates in the locus coeruleus	132	(2)
The cellular effects of norepinephrine and epinephrine are mediated by α- and β-adrenergic receptors	134	(1)
Adrenergic agonists can stimulate arousal and eating behavior	134	(1)
A number of medications work by stimulating or inhibiting peripheral adrenergic receptors	135
Parkinson's Disease---A ``Radical'' Death of Dopaminergic Neurons?	126	(4)
Using ``Gene Knockout'' Animals to Study the Dopaminergic System	130	(9)
Acetylcholine and Serotonin	139	(24)
Acetylcholine	140	(1)
Acetylcholine Synthesis, Release, and Inactivation	140	(4)
Acetylcholine synthesis is catalyzed by the enzyme choline acetyltransferase	140	(1)
Many different drugs and toxins can alter acetylcholine storage and release	140	(1)
Acetylcholinesterase is responsible for acetylcholine breakdown	141	(3)
Organization and Function of the Cholinergic System	144	(7)
Cholinergic neurons play a key role in the functioning of both the peripheral and central nervous systems	144	(2)
There are two acetylcholine receptor subtypes, nicotinic and muscarinic	146	(5)
Serotonin	151	(1)
Serotonin Synthesis, Release, and Inactivation	151	(4)
Serotonin synthesis is regulated by the activity of tryptophan hydroxylase and the availability of the serotonin precursor tryptophan	151	(2)
The processes that regulate storage, release, and inactivation are similar for serotonin and the catecholamines	153	(2)
Organization and Function of the Serotonergic System	155
The serotonergic system originates from cell bodies in the brain stem and projects to all forebrain areas	155	(2)
There is a large family of serotonin receptors, most of which are metabotropic	157
Botulinum Toxin---Deadly Poison, Therapeutic Remedy, and Cosmetic Aid	142	(6)
Alzheimer's Disease---A Tale of Two Proteins	148	(8)
Fen--Phen and the Fight against Fat	156	(7)
Glutamate and GABA	163	(22)
Glutamate	164	(1)
Glutamate Synthesis, Release, and Inactivation	164	(2)
Neurons generate glutamate from the precursor glutamine	164	(1)
Glutamate is released from vesicles and removed from the synaptic cleft by both neuronal and glial transport systems	164	(2)
Organization and Function of the Glutamatergic System	166	(10)
Glutamate is the neurotransmitter used in many excitatory pathways in the brain	166	(1)
Both ionotropic and metabotropic receptors mediate the synaptic effects of glutamate	167	(2)
NMDA receptors play a key role in learning and memory	169	(4)
High levels of glutamate can be toxic to nerve cells	173	(3)
GABA	176	(1)
GABA Synthesis, Release, and Inactivation	176	(2)
GABA is synthesized by the enzyme glutamic acid decarboxylase	176	(1)
Specific transporter proteins are used to transport GABA into synaptic vesicles and nerve terminals following release	176	(2)
Organization and Function of the GABAergic System	178
Some GABAergic neurons are interneurons, while others are projection neurons	178	(1)
The actions of GABA are mediated by ionotropic GABAA receptors and metabotropic GABAB receptors	178
Role of Glutamate Receptors in Long-Term Potentiation	170	(10)
What Is the Endogenous Ligand for the Benzodiazepine Receptor?	180	(5)
Drug Abuse, Dependence, and Addiction	185	(30)
Introduction to Drug Abuse and Addiction	186	(4)
Drugs of abuse are widely consumed in our society	186	(1)
Drug use in our society has increased and become more heavily regulated over time	186	(4)
Features of Drug Abuse and Dependence	190	(6)
Drug addiction is a chronic, relapsing behavioral disorder	190	(1)
There are two types of progressions in drug use	191	(1)
Which drugs are the most addictive?	192	(4)
Models of Drug Abuse and Dependence	196	(11)
The physical dependence model emphasizes the withdrawal symptoms associated with drug abstinence	196	(2)
The positive reinforcement model is based on the rewarding and reinforcing effects of abused drugs	198	(4)
Two recent approaches to drug addiction are the incentive-sensitization and opponent-process models	202	(2)
The disease model treats addiction as a medical disorder	204	(3)
Toward a Comprehensive Model of Drug Abuse and Dependence	207
Three types of factors are involved in experimental substance use	207	(1)
Different factors are involved in the development and maintenance of compulsive substance use	208
The ``Gateway'' Theory of Drug Use	193	(7)
Drugs of Abuse and the Neural Mechanisms of Reward	200	(15)
Alcohol	215	(30)
Psychopharmacology of Alcohol	216	(15)
Alcohol has a long history of use	216	(1)
What is an alcohol and where does it come from?	217	(1)
The pharmacokinetics of alcohol determine its bioavailability	218	(4)
Chronic alcohol use leads to both tolerance and physical dependence	222	(2)
Alcohol affects many organ systems	224	(7)
Neurochemical Effects of Alcohol	231	(6)
Animal models are vital to alcohol research	231	(1)
Alcohol acts on multiple neurotransmitters	232	(5)
Alcoholism	237
Defining alcoholism and estimating its incidence prove difficult	237	(2)
The causes of alcoholism are multimodal	239	(2)
Multiple treatment options provide hope for rehabilitation	241
Fetal Alcohol Syndrome	220	(5)
The Role of Expectation in Alcohol-Enhanced Human Sexual Response	225	(2)
Alcohol and Aggression	227	(18)
The Opiates	245	(30)
Narcotic Analgesics	246	(3)
The opium poppy has a long history of use	246	(1)
Minor differences in molecular structure determine behavioral effects	247	(1)
Bioavailability predicts both physiological and behavioral effects	248	(1)
Opioids have their most important effects on the CNS and on the gastrointestinal tract	248	(1)
Opioid Receptors and Endogenous Neuropeptides	249	(7)
Receptor binding studies identified and localized opioid receptors	249	(1)
Three major opioid receptor subtypes exist	250	(3)
Several families of naturally occurring opioid peptides bind to these receptors	253	(1)
Opiate receptor--mediated cellular changes are inhibitory	254	(2)
Opioids and Pain	256	(4)
The two components of pain have distinct features	256	(2)
Opioids inhibit pain transmission at spinal and supraspinal levels	258	(2)
Opioid Reinforcement, Tolerance, and Dependence	260	(6)
Animal testing shows significant reinforcing properties	260	(1)
Dopaminergic and nondopaminergic components contribute to opioid reinforcement	261	(1)
The consequences of long-term opiate use include tolerance, sensitization, and dependence	262	(2)
Several brain areas contribute to the opioid abstinence syndrome	264	(1)
Neurobiological adaptation and rebound constitute tolerance and withdrawal	264	(1)
Environmental cues have a role in tolerance, drug abuse, and relapse	265	(1)
Treatment Programs for Opiate Addiction	266
Detoxification is the first step in the therapeutic process	269	(1)
Treatment goals and programs rely on pharmacological support and counseling	269
Opiate Bioassay	251	(16)
Role of NMDA Receptors in Tolerance and Dependence	267	(4)
Narcotics Anonymous	271	(4)
Psychomotor Stimulants: Cocaine and the Amphetamines	275	(28)
Cocaine	276	(1)
Background and History	276	(1)
Basic Pharmacology of Cocaine	277	(2)
Mechanisms of Cocaine Action	279	(1)
Acute Behavioral and Physiological Effects of Cocaine	280	(6)
Cocaine stimulates mood and behavior	280	(1)
Cocaine's physiological effects are mediated by the sympathetic nervous system	281	(1)
Dopamine plays a key role in the subjective and behavioral effects of cocaine and other psycho-stimulants	282	(1)
Brain imaging allows researchers to explore the neural mechanisms of psychostimulant action in human subjects	283	(2)
The behavioral and subjective effects of psycho-stimulants involve activation of several DA receptor subtypes	285	(1)
Cocaine Abuse and the Effects of Chronic Cocaine Exposure	286	(6)
Experimental cocaine use may escalate over time to a pattern of cocaine abuse and dependence	286	(1)
Chronic psychostimulant exposure can give rise to tolerance or sensitization	286	(2)
Binge cocaine use has been linked to a specific abstinence syndrome	288	(1)
Repeated or high-dose cocaine use can have serious health consequences	288	(1)
Pharmacological, behavioral, and psychosocial methods are used to treat cocaine abuse and dependence	288	(4)
The Amphetamines	292	(1)
Background and History	292	(2)
Basic Pharmacology of Amphetamine	294	(1)
Mechanisms of Amphetamine Action	294	(1)
Behavioral and Neural Effects of Amphetamine	295	(1)
Amphetamine is a psychostimulant that has therapeutic uses	295	(1)
High doses or chronic use of amphetamine or methamphetamine can cause psychotic reactions as well as brain damage	295	(1)
MDMA---The Entactogenic Amphetamine	296
Your Brain on Cocaine	289	(8)
Psychostimulants and ADHD	297	(6)
Nicotine and Caffeine	303	(24)
Nicotine	304	(1)
Background and History	304	(1)
Basic Pharmacology of Nicotine and Its Relationship to Smoking	304	(2)
Mechanisms of Action	306	(1)
Behavioral and Physiological Effects	307	(6)
Nicotine elicits different mood changes in smokers compared to nonsmokers	307	(1)
Nicotine enhances cognitive function	307	(2)
Nicotine's reinforcing effects are mediated by activation of the mesolimbic dopamine system	309	(1)
Nicotine produces a wide range of physiological effects	309	(1)
Nicotine is a toxic substance that can be fatal at high doses	310	(1)
Chronic exposure to nicotine induces tolerance and dependence	310	(3)
Cigarette Smoking	313	(6)
How many people smoke, and who are they?	313	(1)
Cigarette smokers progress through a series of stages in their smoking behavior	314	(1)
Why do smokers smoke?	314	(2)
Smoking is a major cause of illness and premature death	316	(1)
Behavioral and pharmacological strategies are used to treat tobacco dependence	317	(2)
Caffeine	319	(1)
Background	319	(1)
Basic Pharmacology of Caffeine	319	(1)
Behavioral and Physiological Effects	320	(1)
Acute subjective and behavioral effects of caffeine depend on dose and prior exposure	320	(1)
Regular caffeine use leads to tolerance and dependence	321	(1)
Mechanisms of Action	321
Why Do Tobacco Plants Make Nicotine?	311	(12)
Is Caffeine a Substance of Abuse?	323	(4)
Marijuana and the Cannabinoids	327	(20)
Background and History of Marijuana	328	(1)
Basic Pharmacology of Marijuana	329	(2)
Mechanisms of Action	331	(2)
Cannabinoid effects are mediated by cannabinoid receptors	331	(1)
Endocannabinoids are cannabinoid agonists synthesized by the brain	331	(2)
Acute Behavioral and Physiological Effects of Cannabinoids	333	(7)
Cannabis consumption produces a dose-dependent state of intoxication in humans	333	(4)
Marijuana use can lead to deficits in cognition and psychomotor performance	337	(1)
Animals show a variety of behavioral and physiological responses to cannabinoid administration	337	(1)
Cannabinoids are reinforcing to both humans and animals	338	(2)
Cannabis Abuse and the Effects of Chronic Cannabis Exposure	340
Cannabis use typically begins in adolescence and peaks during young adulthood	340	(1)
Tolerance and dependence can develop from chronic cannabinoid exposure	341	(2)
Chronic cannabis use may lead to adverse behavioral and health effects	343
Therapeutic Uses of Cannabinoids	334	(10)
Does Chronic Cannabis Use Cause Persistent Cognitive Deficits?	344	(3)
Hallucinogens, PCP, and Ketamine	347	(18)
Hallucinogenic Drugs	348	(1)
Mescaline	348	(1)
Mescaline is obtained from the peyote cactus	348	(1)
Psilocybin, DMT, and 5-MeO-DMT	348	(2)
``Magic mushrooms'' are the source of psilocybin and other hallucinogens	348	(2)
Other naturally occurring hallucinogens include DMT and 5-MeO-DMT	350	(1)
LSD	350	(2)
LSD is a synthetic compound based on ergot alkaloids	350	(2)
Pharmacology of Hallucinogenic Drugs	352	(6)
Different hallucinogenic drugs vary in potency but have a similar time course of action	352	(1)
Hallucinogens produce a complex set of psychological and physiological responses	352	(1)
Hallucinogenic drugs share a common indoleamine or phenethylamine structure	353	(1)
Hallucinogens are 5-HT2 receptor agonists	354	(2)
What is the neural mechanism by which hallucinations are produced?	356	(1)
Hallucinogenic drugs cause problems for some users	356	(2)
PCP and Ketamine	358	(1)
Background and History	358	(1)
Pharmacology of PCP and Ketamine	358
PCP and ketamine produce a state of dissociation	358	(1)
PCP and ketamine exhibit potent reinforcing effects	359	(1)
PCP and ketamine are noncompetitive antagonists of NMDA receptors	360	(1)
Ketamine is an increasingly popular drug of abuse	360	(2)
PCP and ketamine have provided new insights into the neurochemistry of schizophrenia	362
The Discovery of LSD	351	(10)
Getting High on Cough Syrup	361	(4)
Inhalants, GHB, and Anabolic-Androgenic Steroids	365	(20)
Inhalants	366	(1)
Background	366	(1)
Behavioral and Neural Effects	367	(2)
Many inhalant effects are similar to alcohol intoxication	367	(1)
Rewarding and reinforcing effects have been demonstrated in animals	367	(1)
Inhalants reduce central nervous system (CNS) excitability by acting on specific ionotropic receptors	367	(1)
Significant health risks are associated with inhalant abuse	368	(1)
Gamma-Hydroxybutyrate	369	(1)
Background	369	(1)
Behavioral and Neural Effects	370	(5)
GHB is a CNS-depressant and behaviorally sedating drug	370	(2)
Evidence for GHB reinforcement in animal studies has been inconsistent	372	(1)
There are two major hypotheses concerning the mechanism of action of GHB	372	(1)
GHB use and abuse has been growing	373	(2)
Anabolic-Androgenic Steroids	375	(1)
Background and History	375	(3)
Anabolic steroids are structurally related to testosterone	375	(1)
Anabolic steroids were developed to help build muscle mass and enhance athletic performance	376	(2)
Anabolic steroids are taken in specific patterns and combinations	378	(1)
Pharmacology of Anabolic Steroids	378
The mechanism of action of anabolic steroids is not fully understood	378	(1)
Many adverse side effects are associated with anabolic steroid use	379	(1)
Do anabolic steroids cause dependence?	380
``Date Rape'' Drugs	371	(10)
Anabolic Steroids and ``Roid Rage''	381	(4)
Affective Disorders	385	(26)
Characteristics of Affective Disorders	386	(6)
Major depression damages the quality of life	386	(1)
In bipolar disorder moods alternate from mania to depression	387	(1)
Risk factors for mood disorders are biological and environmental	387	(5)
Animal Models of Depression	392	(2)
Therapies for Affective Disorders	394	(7)
Monoamine oxidase inhibitors are the oldest antidepressant drugs	395	(2)
Tricyclic antidepressants are highly effective	397	(1)
Second-generation antidepressants have different side effects	398	(1)
Third-generation antidepressants have distinctive mechanisms of action	399	(1)
Electroconvulsive therapy is safe and highly effective	399	(1)
Transcranial magnetic stimulation is easy to administer	399	(1)
Drugs for treating bipolar disorder stabilize the highs and the lows	399	(2)
Neurochemical Basis of Mood Disorders	401	(5)
Serotonin dysfunction contributes to mood disorders	402	(3)
Norepinephrine activity is altered by antidepressants	405	(1)
Norepinephrine and serotonin modulate one another	405	(1)
Neurobiological Models of Depression	406
Mood Disorders and Creativity	388	(5)
Sleep Deprivation Therapy	393	(1)
Stress--Diathesis Model of Depression	394	(17)
Anxiety Disorders	411	(30)
Characteristics of Anxiety Disorders	412	(8)
Anxiety is important for survival	412	(1)
Anxiety disorders are different from everyday worry	412	(6)
Animal models of anxiety are useful for drug testing	418	(2)
Drugs for Treating Anxiety	420	(10)
Barbiturates are the oldest sedative hypnotics	421	(2)
Benzodiazepines are highly effective for anxiety reduction	423	(5)
Second-generation anxiolytics produce distinctive clinical effects	428	(1)
Antidepressants relieve anxiety and depression	429	(1)
Neurochemical Basis of Anxiety and Anxiolytics	430
Multiple neurotransmitters mediate anxiety	431
Neurobiological Model of OCD	419	(6)
Treating Insomnia	425	(11)
Early Experience and Stress	436	(5)
Schizophrenia	441	(28)
Characteristics of Schizophrenia	442	(3)
There is no defining cluster of schizophrenic symptoms	442	(3)
Long-term outcome depends on pharmacological treatment	445	(1)
Preclinical Models of Schizophrenia	445	(2)
Classic Neuroleptics and Atypical Antipsychotics	447	(11)
Phenothiazines and butyrophenones are traditional neuroleptics	447	(4)
Dopamine receptor antagonism is responsible for antipsychotic action	451	(2)
Side effects are directly related to neurochemical action	453	(3)
Atypical antipsychotics are distinctive in several ways	456	(2)
Etiology of Schizophrenia	458	(5)
Abnormalities of brain structure and function occur in individuals with schizophrenia	458	(2)
Genetic, environmental, and developmental factors interact	460	(3)
Neurochemical Models of Schizophrenia	463
Abnormal dopamine function contributes to schizophrenic symptoms	463	(2)
The neurodevelopmental model integrates anatomical and neurochemical evidence	465	(2)
Glutamate and other neurotransmitters contribute to symptoms	467
The Functional Neuroanatomy of Hallucinations	443	(5)
Animal Model---Prepulse Inhibition of Startle	448	(16)
The Genain Quadruplets	464	(5)
Glossary	469	(22)
Illustration Credits	491	(2)
References	493	(22)
Author Index	515	(14)
Subject Index	529