Professional Documents
Culture Documents
Original PDF Psychopharmacology Drugs The Brain and Behavior 3rd Edition
Original PDF Psychopharmacology Drugs The Brain and Behavior 3rd Edition
Original PDF Psychopharmacology Drugs The Brain and Behavior 3rd Edition
1 Principles of Pharmacology 3
Cells of the Nervous System 46 Local potentials are small, transient changes in
membrane potential 60
Neurons have three major external features 46
Sufficient depolarization at the axon hillock opens voltage-
Box 2.1 The Cutting Edge Embryonic Stem Cells 47
gated Na+ channels, producing an action potential 61
Characteristics of the cell membrane are critical for
Drugs and poisons alter axon conduction 63
neuron function 54
Glial cells provide vital support for neurons 55 Organization of the Nervous System 65
Box 2.2 Of Special Interest Astrocytes 56 Box 2.3 The Cutting Edge Finding Your Way in the
Nervous System 65
Electrical Transmission within a Neuron 58
The nervous system comprises the central and peripheral
Ion distribution is responsible for the cell’s resting divisions 66
potential 58
CNS functioning is dependent on structural features 68
viii Contents
The CNS has six distinct regions reflecting embryological The cerebral cortex is divided into four lobes, each
development 70 having primary, secondary, and tertiary areas 76
Box 2.4 Of Special Interest Neuroendocrine Response to Rat and human brains have many similarities and
Stress 76 some differences 79
Research Methods for Evaluating the Brain Multiple Neurobiological Techniques for Assessing
and Behavior 118 the CNS 134
Techniques in Behavioral Pharmacology 118 Stereotaxic surgery is needed for accurate in vivo
measures of brain function 134
Evaluating Animal Behavior 118 Neurotransmitters, receptors, and other proteins can
Animal testing needs to be valid and reliable to be quantified and visually located in the CNS 138
produce useful information 118 New tools are used for imaging the structure and
A wide variety of behaviors are evaluated by function of the brain 145
psychopharmacologists 120 Genetic engineering helps neuroscientists to ask
Box 4.1 Pharmacology in Action Using the Three- and answer new questions 150
Chamber Social Interaction Test 125 Box 4.3 Pharmacology in Action Transgenic Model
Box 4.2 Clinical Applications Drug Testing for of Huntington’s Disease 153
FDA Approval 131 Behavioral and neuropharmacological methods
complement one another 155
Techniques in Neuropharmacology 134
Contents ix
5 Catecholamines 159
Catecholamine Synthesis, Release, and There are five main subtypes of dopamine receptors
Inactivation 160 organized into D1- and D2-like families 171
Tyrosine hydroxylase catalyzes the rate-limiting step Dopamine receptor agonists and antagonists affect
in catecholamine synthesis 160 locomotor activity and other behavioral functions 172
Box 5.2 The Cutting Edge Using Molecular Genetics to
Catecholamines are stored in and released from
Study the Dopaminergic System 174
synaptic vesicles 161
Catecholamine inactivation occurs through the Organization and Function of the
combination of reuptake and metabolism 164 Noradrenergic System 177
Organization and Function of the Norepinephrine is an important transmitter in both
Dopaminergic System 166 the central and peripheral nervous systems 177
Norepinephrine and epinephrine act through α- and
Two important dopaminergic cell groups are found
β-adrenergic receptors 178
in the midbrain 166
The central noradrenergic system plays a significant
Ascending dopamine pathways have been implicated
role in arousal, cognition, and the consolidation of
in several important behavioral functions 167
emotional memories 179
Box 5.1 Clinical Applications Mutations That Affect
Dopamine Neurotransmission 168 Several medications work by stimulating or inhibiting
peripheral adrenergic receptors 183
6 Serotonin 189
Serotonin Synthesis, Release, and Inactivation 190 The serotonergic system originates in the brainstem
and projects to all forebrain areas 196
Serotonin synthesis is regulated by enzymatic activity and
precursor availability 190 The firing of dorsal raphe serotonergic neurons varies
with behavioral state and in response to rewards and
Similar processes regulate storage, release, and punishments 197
inactivation of serotonin and the catecholamines 192
There is a large family of serotonin receptors, most of which
Box 6.1 History of Psychopharmacology “Ecstasy”—
are metabotropic 198
Harmless Feel-Good Drug, Dangerous Neurotoxin, or
Miracle Medication? 193 Multiple approaches have identified several behavioral and
physiological functions of serotonin 200
Organization and Function of the Box 6.2 The Cutting Edge Serotonin and
Serotonergic System 196 Aggression 203
7 Acetylcholine 213
Introduction to Drug Abuse and Addiction 266 Drug dependence leads to withdrawal symptoms when
abstinence is attempted 280
Drugs of abuse are widely consumed in our society 266
Discriminative stimulus effects contribute to drug-seeking
Drug use in our society has increased and has become more behavior 282
heavily regulated over time 267
Genetic factors contribute to the risk for addiction 283
Features of Drug Abuse and Addiction 270 Psychosocial variables also contribute to addiction risk 285
Drug addiction is considered to be a chronic, relapsing The factors contributing to drug addiction can be
behavioral disorder 270 combined into a biopsychosocial model 287
There are two types of progression in drug use 272
The Neurobiology of Drug Addiction 289
Box 9.1 Of Special Interest Should the Term Addiction
Be Applied to Compulsive Behavioral Disorders That Don’t Drug reward and incentive salience drive the binge–
Involve Substance Use? 273 intoxication stage of drug use 289
Which drugs are the most addictive? 275 The withdrawal/negative affect stage is characterized
by stress and by the recruitment of an antireward
Factors That Influence the Development circuit 292
and Maintenance of Drug Abuse and The preoccupation/anticipation stage involves
Addiction 276 dysregulation of prefrontal cortical function and
The addiction potential of a substance is influenced by corticostriatal circuitry 294
its route of administration 277 Molecular neuroadaptations play a key role in the
Most abused drugs exert rewarding and reinforcing transition to an addicted state 296
effects 277 Is addiction a disease? 299
Contents xi
10 Alcohol 307
Nicotine 430 Nicotine exerts both reinforcing and aversive effects 436
Nicotine produces a wide range of physiological
Background and History 430 effects 438
Basic Pharmacology of Nicotine and Its Relationship Nicotine is a toxic substance that can be fatal at high
to Smoking 431 doses 439
Features of tobacco smoking and nicotine Chronic exposure to nicotine induces tolerance and
pharmacokinetics 431 dependence 440
Features of e-cigarette vaping and nicotine Cigarette Smoking and Vaping 443
pharmacokinetics 431
What percentage of the population are current users of
Nicotine metabolism 432 tobacco and/or e-cigarettes? 443
Mechanisms of Action 432 Nicotine users progress through a series of stages in their
pattern and frequency of use 444
Behavioral and Physiological Effects 433 Box 13.1 The Cutting Edge How Safe Are
Nicotine elicits different mood changes in smokers E-cigarettes? 446
compared with nonsmokers 434 Why do smokers smoke and vapers vape? 447
Nicotine enhances cognitive function 434 Smoking is a major health hazard and a cause of
premature death 450
Contents xiii
Behavioral and pharmacological strategies are Acute subjective and behavioral effects of caffeine
used to treat tobacco dependence 451 depend on dose and prior exposure 456
Mechanisms of Action 472 Cannabis Abuse and the Effects of Chronic Cannabis
Exposure 484
Cannabinoid effects are mediated by cannabinoid
receptors 472 Chronic use of cannabis can lead to the development
of a cannabis use disorder 485
Pharmacological and genetic studies reveal the
functional roles of cannabinoid receptors 473 Chronic cannabis use can lead to adverse behavioral,
neurobiological, and health effects 489
Endocannabinoids are cannabinoid receptor agonists
synthesized by the body 474 Box 14.1 Of Special Interest Beyond Cannabis:
The Rise of Synthetic Cannabinoids 495
PCP and Ketamine 515 PCP and ketamine have significant abuse potential 517
Use of PCP, ketamine, or related drugs can cause a
Background and History 515 variety of adverse consequences 519
Pharmacology of PCP and Ketamine 516 Box 15.2 Pharmacology In Action Getting High on
Cough Syrup 520
PCP and ketamine produce a state of dissociation 516
Novel therapeutic applications have been proposed for
PCP and ketamine are noncompetitive antagonists of ketamine 522
NMDA receptors 517
Neurobiology of Anxiety 560 Drugs for Treating Anxiety, OCD, and PTSD 587
What is anxiety? 560 Barbiturates are the oldest sedative–hypnotics 588
The amygdala is important to emotion-processing Benzodiazepines are highly effective for anxiety
circuits 561 reduction 590
Multiple neurotransmitters mediate anxiety 564 Second-generation anxiolytics produce distinctive
Box 17.1 The Cutting Edge Neural Mechanism clinical effects 595
Responsible for High Tonic Cell Firing Mediating Antidepressants relieve anxiety and depression 596
Anxiety 566
Many novel approaches to treating anxiety are being
Genes and environment interact to determine the tendency developed 597
to express anxiety 574
The effects of early stress are dependent on timing 576
The effects of early stress vary with gender 577
Characteristics of Anxiety Disorders 579
Characteristics of Schizophrenia 634 Box 19.1 The Cutting Edge Epigenetic Modifications
and Risk for Schizophrenia 642
There is no defining cluster of schizophrenic
symptoms 634 Preclinical Models of Schizophrenia 646
Etiology of Schizophrenia 636 Box 19.2 Pharmacology In Action
The Prenatal Inflammation Model of Schizophrenia 648
Abnormalities of brain structure and function occur in
individuals with schizophrenia 636 Neurochemical Models of Schizophrenia 650
Genetic, environmental, and developmental factors Abnormal dopamine function contributes to
interact 639 schizophrenic symptoms 650
xvi Contents
The neurodevelopmental model integrates anatomical and Dopamine receptor antagonism is responsible for
neurochemical evidence 651 antipsychotic action 655
Glutamate and other neurotransmitters contribute to Side effects are directly related to neurochemical
symptoms 652 action 657
Classic Neuroleptics and Atypical Atypical antipsychotics are distinctive in several ways 660
Antipsychotics 650 Practical clinical trials help clinicians make decisions
about drugs 663
Phenothiazines and butyrophenones are classic
neuroleptics 654 There are renewed efforts to treat the cognitive
symptoms 664
Parkinson’s Disease and Alzheimer’s Box 20.1 The Cutting Edge Alzheimer’s Disease:
Disease 672 It’s all in your gut??? 684
Glossary G-1
References R-1
Author Index AI-1
Subject Index SI-1
Preface
When we wrote the preface to the Second Edition of will become apparent that new medications for these
Psychopharmacology: Drugs, the Brain, and Behavior, we disorders are being introduced at a slower rate than
were struck by the many exciting developments in the expected, despite ongoing research that continues to
field and the remarkable rate of progress elucidating identify potential new molecular targets for pharma-
the underlying neurobiological mechanisms of psycho- cotherapy. For this reason, we must admit that excit-
active drug action. This has not changed over the 5 ing advances in understanding the basic structure and
years since the publication of that edition. The entire function of the nervous system have not yet led to sim-
field of neuroscience, including neuropsychopharma- ilar progress in treating, much less “curing,” disorders
cology, continues to be driven by technical advances. of this system. We came to the same conclusion when
Using optogenetics, neurobiologists can activate or writing the preface to the Second Edition, so it’s disap-
suppress anatomically and molecularly defined popu- pointing that the hoped-for surge in medication devel-
lations of nerve cells with amazing temporal precision. opment failed to occur during the intervening period.
Neuropharmacologists can visualize the 3-dimensional As before, this new edition of the text is complete-
structure of neurotransmitter receptors, enabling syn- ly updated to incorporate the latest research findings,
thetic chemists to design novel agonist or antagonist methodological advances, and novel drugs of abuse.
drugs with much greater selectivity than could have Regarding the latter, illicit drug labs in the United
been possible before. And huge projects like the Human States and abroad are working hard to turn out mas-
Connectome Project (www.humanconnectomeproject. sive amounts of recreational drugs, whether already
org) are using the most advanced neuroimaging tech- known compounds such as cocaine or fentanyl, or
niques to map the detailed circuitry of the living human novel synthetic compounds that can only be identi-
brain. Because of these technical innovations, we con- fied by submitting drug seizures to advanced forensic
tinue to add new information to Chapter 4, on Methods laboratories for chemical analysis. The national drug
of Research in Psychopharmacology. Readers may choose epidemic involving fentanyl, heroin, and other opioid
to go through the chapter in its entirety to familiarize compounds is discussed in Chapter 11. New and, in
themselves with all of the neuropharmacological and some cases, highly dangerous stimulant and cannabi-
behavioral methods reviewed, or they may choose to noid drugs are introduced in Chapters 12, 14, and 15
use the chapter as a reference source when they en- respectively. Most chapters have new opening vignettes
counter an unfamiliar method in one of the book’s later and breakout boxes, and new photographs, drawings,
chapters. and graphs have been added to bring attention both
Development and introduction of new pharma- to updated material and to completely new topic areas
ceutical compounds continues as well, although the for discussion.
emphasis has somewhat shifted away from the large Importantly, in preparing this next edition of the
pharmaceutical companies to a greater reliance on book we have maintained our conviction that a deep
drug discovery efforts by researchers at universities understanding of the relationship between drugs and
and medical centers. Statistics show that development behavior requires basic knowledge of how the nervous
of new drugs for CNS disorders (e.g., schizophrenia, system works and how different types of drugs interact
depression, and Alzheimer’s disease) costs more than with nervous system function (i.e., mechanisms of drug
for other kinds of disorders, and the failure rate is sig- action). We have also continued to present the methods
nificantly higher. These data have caused many of the and findings from behavioral pharmacological studies
large companies to downsize their CNS drug discovery using animal models alongside key studies from the
programs. As you read the chapters on drug addiction, human clinical research literature. Pharmacologists
mental disorders, and neurodegenerative disorders, it must depend on in vitro preparations and laboratory
xviii Preface
animal studies for determining mechanisms of drug systems most often associated with psychoactive drug
action, for screening new compounds for potential ther- effects, and presentation of their neurochemistry, anat-
apeutic activity, and, of course, for basic toxicology and omy, and function lays the groundwork for the chap-
safety testing. In cases in which clinical trials have al- ters that follow. Chapters 9 through 16 cover theories
ready been performed based on promising preclinical and mechanisms of drug addiction and all the major
results, both sets of findings are presented. In other substances of abuse. Finally, Chapters 17 through 20
instances in which clinical trials had not yet been un- consider the neurobiology of neuropsychiatric and neu-
dertaken at the time of our writing, we have striven to rodegenerative disorders and the drugs used to treat
point you toward new directions of drug development these disorders. Among the neuropsychiatric disor-
so that you can seek out the latest information using ders, special emphasis is placed on affective disorders
your own research efforts. such as major depression and bipolar disorder, various
A new point of emphasis in the text concerns neural anxiety disorders, and schizophrenia. Bulleted interim
circuits as mediators of behavior and as targets of drug summaries highlight the key points made in each part
action. As implied above in referring to the Human of the chapter. New to this edition, study questions are
Connectome Project, focusing on circuits instead of provided at the end of each chapter to assist students
cells as the nervous system’s functional units is the con- in reviewing the most important material. Finally, a
temporary way to think about how our brains control dedicated website for the book (oup-arc.com/access/
our actions, and how drugs, whether recreational or meyer-3e) is available that offers Web Boxes (advanced
medicinal, alter our subjective awareness and behavior. topics for interested readers), study resources such as
The Third Edition of Psychopharmacology: Drugs, the flashcards, web links, and animations that visually
Brain, and Behavior retains the same four-section orga- illustrate key neurophysiological and neurochemical
nization as the previous editions. Chapters 1 through 4 processes important for psychopharmacology.
provide extensive foundation materials, including the It has been our privilege in the first two editions
basic principles of pharmacology, neurophysiology of Psychopharmacology: Drugs, the Brain, and Behavior to
and neuroanatomy, cell signaling (primarily synaptic introduce so many students to the study of drugs and
transmission), and current methods in behavioral as- behavior. With this new and updated edition, we hope
sessment and neuropharmacology. An increased use to continue this tradition and perhaps inspire some of
of clinical examples demonstrates the relevance of the you to continue your studies in graduate school and
material to real-life issues. Chapters 5 through 8 de- join the thousands of researchers worldwide who are
scribe key features of major neurotransmitter systems, working to better understand and ultimately defeat ill-
including the catecholamines, serotonin, acetylcholine, nesses like addiction, depression, schizophrenia, and
glutamate, and GABA. These are the neurotransmitter Alzheimer’s disease.
Preface xix
Value Option
eBook
(ISBN 978-1-60535-728-7)
Psychopharmacology, Third Edition is available as
an eBook in several formats, including RedShelf,
VitalSource, and Chegg. All major mobile devices
are supported.
Psychopharmacology
Drugs, the Brain, and Behavior
THIRD EDITION
CHAPTER 1
Sold,
Salt Beef and Pork, 40 Shillings for a
Cask of 2 Cwt.
Bisket, 17s. per hundred
Candles, 6½ per lb. &c.
Exchange 30 per Cent. or more.
I have heard that the Custom-house Books had one year 35000
Hogsheads of Sugar entred, which at 10l. per Hogshead, amounts to
350000l. Every Acre was supposed 10s. a year Profit to the national
Stock of England, besides what the Planter got, and Mouths fed by
it; but I must observe, the Crops of late years have very much failed,
and put many of them under great Necessities. The Soil fertile in the
Age past, seems now growing old, and past its teeming-time; they
endeavour to mend this by a few Cattle kept for the sake of Manure;
few, I say, because Land imploy’d this way, gives not 1/10 its Value.
Wherefore when a thoughtless Man has joined to unlucky Events
and Seasons an inadvertent way of living, he falls a Prey to the more
astronomical Heads of Factors, who supply him with Food and
Necessaries. The Hardships of many Planters at this time, through
such Inclemencies, cannot be better laid open to the Reader, than in
transcribing part of a Sermon, that I am informed was preached by
Command of his Excellency the Governor, May 1734.
A Charity S e r m o n at Bridgetown,
for the two Parishes, St. Philip, and Christ-Church.