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Drugs and the Neuroscience of Behavior
Second Edition

2
To Lisa and Joe, for your mentorship and friendship

3
Drugs and the Neuroscience of Behavior
An Introduction to Psychopharmacology

Second Edition

Adam Prus
Northern Michigan University

4
FOR INFORMATION:

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any means, electronic or mechanical, including photocopying, recording, or by any
information storage and retrieval system, without permission in writing from the publisher.
Printed in the United States of America.

ISBN 978-1-5063-3894-1

Library of Congress Cataloging-in-Publication Data

Names: Prus, Adam J., author.

5
Title: Drugs and the neuroscience of behavior : an introduction to psychopharmacology / Adam Prus, Northern
Michigan University.

Other titles: Introduction to drugs and the neuroscience of behavior

Description: Second edition. | Los Angeles : SAGE, [2018] | Revision of: An introduction to drugs and the
neuroscience of behavior. 2014. | Includes bibliographical references and index.

Identifiers: LCCN 2016051143 | ISBN 9781506338941 (pbk. : alk. paper)

Subjects: LCSH: Psychopharmacology. | Psychotropic drugs—Side effects.

Classification: LCC RM315 .P718 2018 | DDC 615.7/8—dc23 LC record available at

https://lccn.loc.gov/2016051143

This book is printed on acid-free paper.

Acquisitions Editor: Abbie Rickard

Production Editor: Andrew Olson

Copy Editor: Pam Suwinsky

Typesetter: C&M Digitals (P) Ltd.

Proofreader: Caryne Brown

Indexer: Judy Hunt

Cover Designer: Michael Dubowe

Marketing Manager: Jenna Retana

6
Brief Contents
1. Preface
2. About the Author
3. Chapter 1 • Introduction to Psychopharmacology
4. Chapter 2 • The Nervous System
5. Chapter 3 • Neurotransmission
6. Chapter 4 • Properties of Drugs
7. Chapter 5 • Drugs of Abuse
8. Chapter 6 • Psychostimulants
9. Chapter 7 • Nicotine and Caffeine
10. Chapter 8 • Alcohol
11. Chapter 9 • GHB and Inhalants
12. Chapter 10 • Opioids
13. Chapter 11 • Cannabinoids
14. Chapter 12 • Psychedelic Drugs
15. Chapter 13 • Treatments for Depression and Bipolar Disorder
16. Chapter 14 • Treatments for Anxiety Disorders
17. Chapter 15 • Antipsychotic Drugs
18. References
19. Author Index
20. Subject Index

7
Detailed Contents
Preface
About the Author
1 Introduction to Psychopharmacology
Psychopharmacology
Why Read a Book on Psychopharmacology?
Drugs: Administered Substances That Alter Physiological Functions
Psychoactive Drugs: Described by Manner of Use
Generic Names, Trade Names, and Street Names for Drugs
Drug Effects: Determined by Dose
Pharmacology: Pharmacodynamics, Pharmacokinetics, and Pharmacogenetics
Psychoactive Drugs: Objective and Subjective Effects
Study Designs and the Assessment of Psychoactive Drugs
Validity: Addressing the Quality and Impact of a Study
Animals and Advancing Medical Research
A Lack of Feasible Alternatives
High Predictive Value for Drug Effects in Humans
The Regulation of Animal Research
Animal Rights Activism Seeks to Eliminate Animal Research
Researchers Consider Many Ethical Issues When Conducting Human Research
FROM ACTIONS TO EFFECTS: Therapeutic Drug Development
CHAPTER SUMMARY
KEY TERMS
2 The Nervous System
► Is There More to the Story of Phineas Gage?
Cells in the Nervous System
Neural Communication
Glial Cells: Facilitating Nervous System Functions
The Nervous System: Control of Behavior and Physiological Functions
The Peripheral Nervous System: Controlling and Responding to
Physiological Processes in the Body
The Central Nervous System
Cerebral Blood Flow and Cerebrospinal Fluid
Genes and the Physiological Processes of Cells
► Box 2.1 Genetically Modified Organisms
FROM ACTIONS TO EFFECTS: Gilal Scars and Recovery From Brain
Injury
CHAPTER SUMMARY
KEY TERMS
3 Neurotransmission

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 ► Drugs for Alzheimer’s Disease Alter Acetylcholine Neurotransmission
Electrical Events Within a Neuron and the Release of Neurotransmitters
► Box 3.1 Electrophysiology and Microdialysis
Nerve Impulses: Electrical Potential Changes in Neurons
Resting Potential
Action Potential
Refractory Periods
Propagation of Action Potentials Down Axons
Neurotransmitters: Signaling Molecules for Neuronal Communication
Neurotransmitter Synthesis
Neurotransmitter Storage
Calcium Influx and Neurotransmitter Release
Neurotransmitters Bind to Receptors
Termination of Neurotransmission
Neurotransmission: Neurotransmitter Binding to Receptors
Receptors: Ionotropic or Metabotropic
Different Types of Neurotransmitters and Communication
Glutamate and GABA Are the Most Abundant Neurotransmitters
Monoamine Neurotransmitters: Dopamine, Norepinephrine, Epinephrine, and
Serotonin
Dopamine
Norepinephrine and Epinephrine
Serotonin
Acetylcholine
Neuropeptides: A Large Class of Neurotransmitters
Nitric Oxide: A Unique Neurotransmitter
Other Types of Chemical Transmission in the Nervous System
Neurotrophins
Hormones
FROM ACTIONS TO EFFECTS: Treating Alzheimer’s Disease
CHAPTER SUMMARY
KEY TERMS
4 Properties of Drugs
► Do Environmental Stimuli Contribute to Heroin Tolerance?
Pharmacokinetic Properties and Drug Passage Through the Body
Absorption
Distribution
Biotransformation
Elimination
Pharmacodynamics: Describing the Actions of Drugs
Psychoactive Drugs and Receptors
► Box 4.1 Radioligand Binding for Measuring Receptor Affinity

9
 ► Box 4.2 The [35S]GTPγS Binding Assay Assesses G-Protein Activation
Neurotoxins and Damage to the Nervous System
Adaptations to Chronic Drug Use
FROM ACTIONS TO EFFECTS: Heroin Tolerance and Overdose
CHAPTER SUMMARY
KEY TERMS
5 Drugs of Abuse
► James Olds’s Unexpected Discovery
Regulatory Agencies and Drug Classification
Clinical Definitions and the Diagnosis of Drug Addiction
Theoretical Models and the Features of Drug Addiction
Disease Model of Drug Addiction
Associative Learning Principles Used in Addiction Models
Drive, Opponent-Process Theory, and Incentive-Salience Models of
Drug Addiction
► Box 5.1 Self-Administration
Drugs of Abuse and Reward Circuitry
Drug Abuse and Changes to Learning and Memory Systems
Neurobiology and the Stages of Drug Addiction
Mortality and Drug Addiction
Psychological and Pharmacological Therapies for Treating Drug Dependence
FROM ACTIONS TO EFFECTS: Food Addiction
CHAPTER SUMMARY
KEY TERMS
6 Psychostimulants
► Fleischl and the Neurologist
Psychostimulants: A Large Variety of Substances
Psychostimulants: Herbal Remedies, Prescription Drugs, and Substances of
Abuse
Ephedra
Amphetamines
Methylphenidate
Cathinones
Cocaine
Pharmacokinetics of Psychostimulants
Routes and Forms of Psychostimulant Administration
Biotransformation of Psychostimulants
Elimination of Psychostimulants
Psychostimulants and Monoamine Neurotransmitters
Amphetamines
Methylphenidate and Cathinones
Cocaine

10
 Cocaine- and Amphetamine-Regulated Transcript
Pharmacological Effects of Psychostimulants
Physiological Effects
Behavioral Effects
Subjective Effects
Adverse Effects
► Box 6.1 Drug Discrimination
Psychostimulant Drugs Produce Sensitization and Tolerance
Psychostimulant Addiction
FROM ACTIONS TO EFFECTS: Treatments for Psychostimulant Addiction
CHAPTER SUMMARY
KEY TERMS
7 Nicotine and Caffeine
► Is Nicotine Not Addictive?
Nicotine: Key Psychoactive Ingredient in Tobacco
Discovery of Tobacco
Tobacco Use and Pharmacokinetic Properties
Tobacco Use and Nicotine Absorption
Nicotine Absorption Through Lung and Oral Tissues
Distribution and Biotransformation of Nicotine
Elimination of Nicotine
Nicotine and Nervous System Functioning
Nicotine’s Potent Pharmacological Effects
Nicotine’s Effects on Cardiovascular Function and Appetite
Nicotine Affects Movement and Cognitive Functioning
Nicotine’s Positive and Negative Subjective Effects
Adverse Effects of Tobacco Use
► Box 7.1 Conditioned Taste Aversion
Nicotine and Psychological Dependence
Environmental, Genetic, and Receptor Differences Between Light and Heavy
Tobacco Users
FROM ACTIONS TO EFFECTS: Why People Smoke and How They Quit
Caffeine
Caffeine and Related Compounds in Plants
Caffeine Has an Ancient History
Caffeine Absorption, Duration, and Interaction With Other Psychoactive
Drugs
Caffeine: Antagonist for Adenosine Receptors
Caffeine: Mild Psychostimulant Effects
Tolerance and Dependence During Sustained Caffeine Use
FROM ACTIONS TO EFFECTS: Why People Consume Caffeinated
Products

11
 CHAPTER SUMMARY
KEY TERMS
8 Alcohol
► “Halfway to Concord” and “Taking Hippocrates’s Grand Elixir”
Alcohol: The Most Commonly Used Depressant Substance
Alcohol Production Through Fermentation and Distillation
The History of Alcohol Consumption
Pharmacokinetic Factors and Alcohol’s Effects
Alcohol and Central Nervous System Functioning
Alcohol and GABAA Receptors
Alcohol and Glutamate Receptors
Alcohol and Calcium
Alcohol and Serotonin Receptors
Alcohol and the Endocannabinoid System
Pharmacological Effects of Alcohol
Types of Drinking and Number of Drinks Consumed
Acute Alcohol Consumption and Cardiovascular and Respiratory
Functioning
Alcohol’s Depressive Effects on Behavior and Cognitive Functioning
Alcohol and Positive Subjective Effects
Severe Adverse Effects of High BAC
Chronic Heavy Alcohol Consumption and Adverse Cardiovascular and
CNS Effects
Alcohol: Tolerance and Sensitization
Alcohol Addiction and Withdrawal
Treating Alcohol Addiction
FROM ACTIONS TO EFFECTS: Hangover
CHAPTER SUMMARY
KEY TERMS
9 GHB and Inhalants
► Did the Revelations of Ancient Greek Oracles Come From Chemical
Inhalants?
Gamma-Hydroxybutyrate
History of GHB
GHB: Natural and Synthetic
Pharmacological Actions of GHB
Pharmacological Effects of GHB
► Box 9.1 Electroencephalography
GHB Overdose and Risk of Addiction
Inhalants
History of Inhalants
Inhalants: Rapid Absorption and Elimination

12
 Pharmacological Actions of Inhalable Solvents
Inhalants: Pharmacological Effects and Interference With Oxygen Intake
FROM ACTIONS TO EFFECTS: Stimulus Properties of GHB and Toluene
CHAPTER SUMMARY
KEY TERMS
10 Opioids
► A “Treatment” for Morphine Addiction?
Opioids: Natural and Synthetic
History of Opium Use
Pharmacokinetic Properties and Opioid Abuse
Opioid Drug Interactions With the Endogenous Opioid System
Opioid Drugs: Classification by Receptor Action
Opioid System Interactions With Reward, Pain, and Stress Systems
Opioid Reinforcing and Analgesic Effects
Opioid Receptor Agonists and Reinforcing Effects
► Box 10.1 Conditioned Place Preference
Opioid Analgesic Effects
Opioid Drugs and Other Therapeutic Effects
Opioid Drugs and Respiratory Function
Tolerance and Dependence With Chronic Opioid Use
FROM ACTIONS TO EFFECTS: Pharmacological Approaches for Treating
Opioid Addiction
CHAPTER SUMMARY
KEY TERMS
11 Cannabinoids
► Should Medical Marijuana Be Legal?
Historical Use of Cannabis
Methods of Cannabis Preparation and Use
Cannabinoid Compounds and the Endocannabinoid System
Cannabinoids and CB1 and CB2 Receptors
Physiological Effects of Cannabinoids
Behavioral Effects of Cannabinoids
Subjective Effects of Cannabinoids
Cannabinoid Tolerance and Dependence
Cannabis and Health Risk
FROM ACTIONS TO EFFECTS: Medical Marijuana
CHAPTER SUMMARY
KEY TERMS
12 Psychedelic Drugs
► Did Hofmann Take a “Trip”?
Hallucinogens
Origins of LSD and Other Hallucinogens

13
 LSD Ingestion and Effects
LSD and the Serotonin Neurotransmitter System
LSD’s Mild Physiological Effects and Profound Hallucinogenic Effects
Hallucinogens and Flashbacks
Mixed Stimulant–Psychedelic Drugs
MDMA Therapeutic and Recreational Use
MDMA Metabolism and the Length of Psychedelic Drug Effects
MDMA and Serotonin and Dopamine Neurotransmission
MDMA’s Psychedelic and Psychostimulant Effects
MDMA’s Adverse Effects
► Box 12.1 Social Interaction Tests
MDMA Use in Psychotherapy
Tolerance and Dependence During Chronic MDMA Use
Recreational Use of Dissociative Anesthetics
Development of Phencyclidine, Ketamine, and Dizocilpine
Absorption and Elimination of Phencyclidine
Phencyclidine’s Effects on Dopamine and Serotonin Neurotransmission
Dissociative Anesthetics and Glutamate Neurotransmission
The Anesthetic and Psychedelic Effects of Dissociative Anesthetics
Dissociative Anesthetics and Schizophrenia-Like Effects
Tolerance, Dependence, and the Use of Dissociative Anesthetics
Other Psychedelic Drugs
FROM ACTIONS TO EFFECTS: Synesthesia
CHAPTER SUMMARY
KEY TERMS
13 Treatments for Depression and Bipolar Disorder
► Did Reserpine Revolutionize the Study of Antidepressant Medications?
Mental Disorders
Depression
The Prevalence of Depressive Disorders
Neuroimaging Techniques and Functioning Differences in Depression
Antidepressant Drugs
► Box 13.1 Animal Behavioral Models for Identifying Antidepressant Drugs
Limitations in Antidepressant Drug Effectiveness and Development
Combination Strategies for Treating Depression With Antidepressant
Drugs
Combining Psychotherapy and Pharmacotherapy for Treating
Depression
Antidepressant Drugs and Monoamine Neurotransmitter Systems
Bipolar Disorder
Neurobiology of Bipolar Disorder
Mood Stabilizers, Anticonvulsants, Antipsychotics, and Antidepressants

14
 for Bipolar Disorder
FROM ACTIONS TO EFFECTS: Pharmacogenetic Factors and Treatment
Response in Depression
CHAPTER SUMMARY
KEY TERMS
14 Treatments for Anxiety Disorders
► Was Miltown Too Good to Be True?
Anxiety Disorders
Structures Involved in Fear and Anxiety
► Box 14.1 Optogenetics
Anxious Feelings, the Amygdala, and the Sympathetic Nervous System
► Box 14.2 Animal Models for Screening Anxiety Treatments
Stress and the HPA Axis
Anxiolytic and Antidepressant Drugs and the Treatment of Anxiety
Barbiturates
Benzodiazepines
Z-drugs
Anticonvulsant Drugs for Treating Anxiety Disorders
Antidepressant Drugs and the Treatment of Anxiety Disorders
Buspirone and the Treatment of Anxiety Disorders
FROM ACTIONS TO EFFECTS: How Do Antidepressant Drugs Reduce
Anxiety?
CHAPTER SUMMARY
KEY TERMS
15 Antipsychotic Drugs
► Kraepelin’s Influence in Distinguishing Neurological From Mental
Disorders
Schizophrenia
► Box 15.1 Prepulse Inhibition
Schizophrenia’s Complex Neurobiological Profile
A Brief History of Schizophrenia and Its Treatment
Neurotransmission Hypotheses for Schizophrenia
Typical and Atypical Antipsychotic Drugs
Typical Antipsychotic Drugs: The First Medications for Schizophrenia
Atypical Antipsychotic Drugs: First-Line Treatments for Schizophrenia
Pharmacological Actions of Atypical Antipsychotic Drugs
Third-Generation Antipsychotic Drugs
Administration Forms for Antipsychotic Drugs
► Box 15.2 Animal Models for Identifying Typical and Atypical
Antipsychotic Drugs: Conditioned Avoidance and Catalepsy
Antipsychotic Drugs and Autism
FROM ACTIONS TO EFFECTS: Antipsychotic Drug Actions and

15
 Neurotransmission in Schizophrenia
CHAPTER SUMMARY
KEY TERMS
References
Author Index
Subject Index

16
Preface

Drugs and the Neuroscience of Behavior: An Introduction to Psychopharmacology, second

edition, provides a broad coverage of the fundamental concepts and principles of
psychopharmacology. These include how drugs enter and travel through the body, the
various actions psychoactive drugs can have in the brain, and the many types of behavioral
and physiological effects brought about by the actions of drugs in the brain. These topics
are presented early in the book and show how they can help us to understand the use,
actions, and effects of different classes of drugs, including psychostimulants, depressants,
cannabis, psychedelics, and drugs used for treating mental disorders.

The first edition of the text came about from my years of teaching and studying
psychopharmacology; in particular, I was influenced by my research training, which
involved everything from bench-top molecular biology work to assessing behavior in lab
rats and mice. The current edition of the textbook continues to emphasize how basic
research findings apply to the effects we find in humans. In doing so, students not only
learn how drugs act on the nervous system to produce pharmacological effects, but they
also learn about the techniques used to study psychoactive drugs.

It’s been only a few years since the first edition was released, but the rapid advancement of
this field has made a revision to the book absolutely necessary. Here’s an example: vaping.
Nicotine vaping became popular soon after the release of the first edition and is now a
major addition to Chapter 7, “Nicotine and Caffeine.” This is one of many major new
topics added to the second edition, all of which I note later in this Preface.

17
How the Materials Are Organized
Like the first edition, the second edition provides a number of features that help to facilitate
the delivery of this material to students. Information in the book is provided in a careful,
step-by-step presentation of information supplemented by illustrations, figures, boxes, and
several unique pedagogical features. These features include the following.

From Actions to Effects

Each chapter ends with a section called “From Actions to Effects.” These sections cover a
topic that brings together information presented in the chapter, providing a way to
assemble multiple topics for addressing a single concept. In particular, these topics focus on
a concept that requires understanding a drug’s actions to account for its effects. These
sections aid in the conceptual understanding of chapter material.

Stop & Check

Stop & Check questions conclude each section in each chapter. These questions allow
students to self-assess their understanding of main points covered in the previous section.

Review!
Chapters include important reminders of facts or concepts covered in previous chapters.
These help integrate the diverse material covered in this text.

Drug Profiles
This a new feature in the second edition that provides important basic information about a
key compound. Information in these profiles includes a drug’s generic name, trade name,
and/or street name and provides a description of its pharmacological actions.

Research Techniques and Methods

Chapters include boxes that cover a research technique or method used in
psychopharmacology research. These boxes model good working science and provide an
easy reference when students come across research findings derived from each technique.
These studies are also important in fostering critical thinking habits in students.

Key Terms

18
Each chapter ends with a list of key terms from the chapter. A definition is provided for
each key term in a combined glossary and index at the end of the book.

Supplementary Materials
The text comes equipped with PowerPoint presentations and a test bank of exam questions
organized by chapter.

19
Changes in the Second Edition
This second edition of Drugs and the Neuroscience of Behavior: An Introduction to
Psychopharmacology provides major changes throughout book, including the addition of
new topics and updated information on past topics.

Major new topics include coverage of:

Chapter 2: Epigenetics
Chapter 3: Optogenetics
Chapter 4: The role of pKa and pH in drug absorption
Chapter 5: Bulimia nervosa
Chapter 6: Sex differences in psychostimulant addiction
Chapter 7: E-cigarettes and vaping
Chapters 6–15: DSM-5 diagnostic criteria for dependence and mental disorders
Chapter 8: Kombucha and different types of beer
Chapter 11: Dabbing and vaping cannabis products
Chapter 12: Timothy Leary
Chapter 13: Gliotransmitters, treatments for fibromyalgia
Chapter 15: Pharmacological treatments for autism spectrum disorder

New findings for topics found in the first edition were provided on:

Chapter 5: The role of the amygdala in drug addiction

Chapter 6: Bath salts
Chapter 7: Tobacco smoke exposure and risk of Alzheimer’s disease
Chapter 8: Changes in glutamate receptor function during chronic alcohol use and
alcohol blackout
Chapter 11: The effectiveness of medical marijuana
Chapter 12: Effectiveness of ketamine for treating depression
Chapter 14: The association between cortisol levels and posttraumatic stress disorder

Here is a more detailed overview of what was added for the second edition.

Chapter 1: Certain safety index, clarifications about study variables, and clinical trial
phases.
Chapter 2: Clarification of information about genetics, new material about
neurogenetics and epigenetics, and more information about the autonomic nervous
system.
Chapter 3: An entire box devoted to optogenetics, and new information about
turnover, neuromodulation, Down syndrome, and conformational changes to
neurotransmitter receptors.

20
Chapter 4: Significant content regarding pharmacokinetics, including equations that
consider a drug’s pKa and the pH levels of the physiological environment, Phase I
and II Biotransformation, the term liberation, and conjugation and conjugation
reaction. Further, new material on allosteric regulation, levodopa, and conditioned
tolerance.
Chapter 5: Consideration of the discordance between state and federal laws regarding
medical marijuana, updated material about DSM-5 (as do all subsequent chapters),
revised and improved material regarding James Olds and Otto Loewi, role of
amygdala in addiction, additional information about 12-step programs, bulimia
nervosa, and some helpful information for readers who may need assistance coping
with drug addiction.
Chapter 6: Updated information on bath salts, and other additions included sex
differences in psychostimulant addiction, information about use of cocaine for nasal
surgeries and severe nose bleeds, and updated statistics on psychostimulant drug use
(all subsequent chapter received updated use statistics).
Chapter 7: Substantially revised material on e-cigarette use and vaping, thirdhand
smoking, greater mortality rates among African Americans, tobacco flue curing,
menthol cigarettes, tobacco smoke exposure and risk of Alzheimer’s disease, why
some first-time smokers become chronic smokers while others do not, material on
how to quit smoking, differences in the success of smoking cessation therapies based
on racial and sex differences, pH of caffeine and degree of absorption, and a
characterization of adenosine.
Chapter 8: Descriptions of different alcoholic beverages, polymorphisms and alcohol
metabolism, changes in NMDA receptor function from chronic alcohol
consumption, updated statistics on binge drinking, different types of blackout,
hormesis, cancer risk from drinking, confabulation, and acamprosate.
Chapter 9: A note about 1,4-Butanediol being an industrial solvent.
Chapter 10: The dramatic increase in heroin use was noted, along with information
about desomorphine, CYP2D6 activity and metabolism of codeine, definition of
opioid overdose, an explanation for why buprenorphine can be prescribed from
doctor’s offices, and a description of morphine as a potential partial agonist.
Chapter 11: Updated information on descriptions of different forms of cannabis,
THC concentrations if different types of cannabis plants, dabbing, personal vaporizer
use of smoking cannabis, relaxed federal regulations on transportation of cannabis,
clarified information on THC and weight gain, risk of schizophrenia from cannabis
use, major additions to behavioral effects of cannabis use, adverse effects from
synthetic cannabis use, and new evidence about effectiveness of medical marijuana.
Chapter 12: New material, including possibility that Salem witch trials were caused
by ergot poisoning, NBOMe drugs, Timothy Leary, effects of chronic hallucinogen
use, use of hallucinogens in psychotherapy, multiple organ failure (regarding
MDMA), effects of phencyclidine at neuromuscular junctions, out-of-body
experience, and effects of dissociative anesthetics on memory.

21
Chapter 13: New prevalence data on differences in depression between men and
women, greater prevalence of aggression in depressed men, predictors of suicide,
higher rates of depression in Alzheimer’s disease, role reserpine played in history of
psychopharmacology, levodopa and the film Awakenings, black box warnings for
antidepressants, sexual side effects, emotional blunting, fibromyalgia, issues
surrounding placebo effects in antidepressant studies, combining psychotherapy and
pharmacotherapy, role of serotonin neurotransmission in antidepressant effects, new
material on ketamine and scopolamine, use of diffusion tensor imaging in bipolar
disorder, and historical information on lithium.
In Chapter 14, more information about differences between anxiety and fear, a
description of how optogenetics was used to activate fear memories, associations
between cortisol levels and PTSD, clarification between sedative and hypnotic,
potential for addiction to benzodiazepines, gliotransmitters, endogenous
benzodiazepines, Z-drugs, and role of serotonin neurotransmission in effectiveness of
drugs for treating anxiety.
Chapter 15: Now has a description of benzodiazepine use for catatonic
schizophrenia, cognitive dysmetria, the long-abandoned theory of the
schizophrenogenic mother, the disputes between Laborit and Deniker, antiemetic
effects of antipsychotic drugs, antipsychotic depot injections, and the use of
antipsychotic drugs for treating autism.

22
Acknowledgments
I am thrilled to have my second edition developed by SAGE Publishing, which has a strong
reputation for high-quality and trusted science textbooks. I am especially thankful for all of
the support from the acquisitions editor of this second edition, Reid Hester, who was
always quick to provide guidance, advice, and even a friendly conversation whenever I
needed it. Abbie Rickard joined the editorial team overseeing the book’s development near
of the end of the project and already has provided great advice on the overall scope of this
text. Editorial assistants provide a tremendous amount of work behind the scenes, and I am
thankful for all of the efforts made by Alex Helmintoller and Morgan Shannon (now an
eLearning Editor at SAGE Publishing). I thank the copyeditor, Pam Suwinsky, who spent
many long evenings taking this from a rough draft to something presentable. The mad dash
to the production finish line was greatly facilitated by the production editor Andrew Olson.
I remain grateful for those who were critical to the development and production of the
previous edition of this book, and in particular, note Ken King and Jon-David Hague. A
number of revisions and corrections suggested for the current edition were provided by
psychopharmacology instructors who were kind enough to spend a great deal of time
reading and commenting on the first edition. I am grateful for their feedback and, of
course, any errors or distortions that may be found in the second edition are entirely my
own.

Kristine Bonacchi-Stigi, Brooklyn College, CUNY

Perry W. Buffington, University of Georgia
Deborah Carroll, Southern Connecticut State University
Amy Coren, Northern Virginia Community College, Alexandria Campus
Drew D’Amore, The College of New Jersey
David DeMatteo, Drexel University
Carol Devolder, St. Ambrose University
Karen K. Glendenning, Fort Valley State University
Evan Hill, University of Nebraska at Kearney
William Jenkins, Mercer University, Macon Campus
Chris Jones, College of the Desert
Michael Kerchner, Washington College
Serena King, Hamline University
Lorenz S. Neuwirth, SUNY Old Westbury
Meghan E. Pierce, University of Nevada, Las Vegas

Of course, the test participants for any textbook are one’s students. I hesitate a bit in listing
those who helped in this regard, since I risk forgetting discussions in the classrooms or
hallways that might have prompted me to write something or change something that I
otherwise may not have considered. With this caveat stated, I point out Ian Buentello,

23
Sigrid Crowel, Brooke Lewis, and Katelin Matazel as raising very interesting points that
helped me in crafting some topics in this book. And finally, I wish to thank my wife
Jennifer and my kids Kendell and Daniel who tolerated the many hours I spent shut in our
home office tapping away at a laptop. To all: thank you!

24
Instructor Teaching Site
A password-protected site, available at www.study.sagepub.com/prus2e, features resources that have been
designed to help instructors plan and teach their course. These resources include an extensive test bank,
chapter-specific PowerPoint presentations, lecture notes, discussion questions to facilitate class discussion,
and links to SAGE journal articles with accompanying article review questions.

25
Student Study Site
A Web-based study site is available at www.study.sagepub.com/prus2e. This site provides access to several
study tools including eFlashcards, web quizzes, and links to full-text SAGE journal articles.

26
About the Author

Dr. Adam Prus

is a professor and head of psychology at Northern Michigan University in Marquette,
Michigan. He earned his PhD in psychology from Virginia Commonwealth
University and a master’s degree in psychology from Western Michigan University.
While in graduate school, Prus also worked as a research technician at a large
pharmaceutical company, where he screened central nervous system drugs using
various biological assays. After earning his PhD, Dr. Prus investigated experimental
antipsychotic drugs as a postdoctoral fellow in the Psychopharmacology Division of
the Department of Psychiatry at Vanderbilt University. Dr. Prus has published
numerous original studies on psychoactive drugs, including studies funded by the

27
National Institute on Mental Illness and private foundations. At NMU, he directs
the Neuropsychopharmacology Laboratory, where he enjoys mentoring
undergraduate and graduate students and spends too much time fixing lab
equipment. When he is not teaching, training students, writing books or conducting
research, Dr. Prus spends time with his wife and two children, and together they
enjoy outdoor activities in Michigan’s Upper Peninsula, where NMU is located.

28
1 Introduction to Psychopharmacology

29
Another random document with
no related content on Scribd:
A businesslike atmosphere filtered through the quiet of the Smokies.
Though wolves and panthers had largely disappeared by 1910, fur
buyers and community traders enjoyed a brisk exchange in mink,
raccoon, fox, and ’possum hides. Oak bark and chestnut wood,
called “tanbark” and “acid wood” because they were sources of
valuable tannic acid, brought $7 per cord when shipped to Asheville
or Knoxville. As the sawmills flourished, makeshift box houses of
vertical poplar and chestnut planks gave way to more substantial
weatherboarded homes of horizontal lengths and tight-fitting frames.
Slick, fancy, buggy-riding “drummers” peddled high-button shoes and
off-color stories. The spacious Wonderland Park Hotel and the
Appalachian Club at Elkmont, and a hunting lodge on Jake’s Creek
graced the once forbidding mountainsides.
Undergirding this development was a growing cash base: peaches
and chestnuts, pork and venison, wax and lard—translated into
money—brought flour and sugar, yarn and needles, tools and
ammunition. Yet in the midst of this new-found activity, many clung to
their old habits. Children still found playtime fun by sliding down hills
of pine needles and “riding” poplar saplings from treetop to treetop.
Hard-shell Baptist preachers, such as the hunter and “wilderness
saddle-bagger” known as “Preacher John” Stinnett, still devoted long
spare hours, and sometimes workdays as well, to reading The Book:
“I just toted my Bible in a tow sack at the handle of my bull tongue
and I studied it at the turn of the furrow and considered it through the
rows.”
But whatever the immediate considerations of the hour happened to
be, logging was the order of the day. From the Big Pigeon River, all
the way to the Little Tennessee, the second generation of timber-
cutters had moved into the Smokies on a grand scale.
The companies, with their manpower, their strategically placed
sawmills, and their sophisticated equipment, produced board feet of
lumber by the millions. The rest of the country, with its increased
demands for paper and residential construction, absorbed these
millions and cried for more. By 1909, when production attained its
peak in the Smokies and throughout the Appalachians, logging
techniques had reached such an advanced state that even remote
stands of spruce and hemlock could be worked with relative ease.
Demand continued unabated and even received a slight boost when
World War I broke out in 1914.

Pages 100-101: Sawmills, such as this one at

Lawson’s Sugar Cove, were quickly set up in one
location and just as quickly moved to another as soon
as the plot was cleared.
National Park Service
High volume covered high costs. The Little River Lumber Company,
perhaps the most elaborate logging operation in the Smokies, cut a
total of two billion board feet. Cherry, the most valuable of the
woods, with its exquisite grain and rich color, was also the scarcest.
Yellow-poplar, that tall, straight tree with a buoyancy that allowed it to
float high, turned out to be the most profitable of all saw timber.
Coniferous forests, the thick, dark regions of pungent spruce and
hemlock, yielded a portion of the company’s output.
Extraction of such proportions was not easy. Timber cruisers combed
the forests, estimating board feet and ax-marking suitable trees.
Three-man saw teams followed the cruisers. One, the “chipper,”
calculated the fall of the tree and cut a “lead” in the appropriate side.
Two sawyers then took over, straining back and forth upon their
crosscut saw until gravity and the immense weight of the tree
finished their job for them. The work was hard and hazardous.
Sometimes, if the lead were not cut properly, the trunk would fall
toward the men; sudden death or permanent injury might result from
the kickback of a doomed tree’s final crash, or from a moment’s
carelessness.
To remove the felled timber, larger companies laid railroad tracks far
up the creeks from their mills. At the eastern edge of the Smokies,
for instance, one such terminus grew into the village of Crestmont,
which boasted a hotel, two movie theaters, and a well-stocked
commissary. Such accommodations seemed a distant cry indeed
from the upper branches of Big Creek, gathering its waters along the
slopes of Mt. Sterling, Mt. Cammerer, and Mt. Guyot. Workers from
improbable distances—even countries “across the waters,” such as
Italy—teamed with the mountain people to push a standard gauge
track alongside the boulder-strewn streams. Bolted onto oaken ties
that were spaced far enough apart to discourage foot travel, the
black rails drove ahead, switched back to higher ground, crossed Big
Creek a dozen times before they reached the flat way station of
Walnut Bottoms.
Dominated by powerful, blunt-bodied locomotives, the railroads gave
rise to stories that were a flavorful blend of pathos and danger.
“Daddy” Bryson and a fireman named Forrester were killed on a
sharp curve along Jake’s Creek of Little River. Although Forrester
jumped clear when the brakes failed to hold, he was buried under an
avalanche of deadly, cascading logs. There were moments of
comedy as well as tragedy. In the same river basin, Colonel
Townsend asked engineer Noah Bunyan Whitehead one day when
he was going to stop putting up all that black smoke from his train.
Bun
answered
: “When
they start
making
white
coal.”
Railroads
could
reach
only so
far,
however.
The most
complex
phase of
the
logging
process
was
“skidding,
” or
bringing
the felled
logs from
inaccessi
ble
distances
to the
waiting
cars. As
the first
step, men
armed
with cant Little River Lumber Company
hooks or
short,
harpoon- Massive steam-powered skidders pulled
like logs in off the hills to a central pile. Then the
peavies, loaders took over and put the logs on trains,
simply which carried them to the mills.
rolled the
logs
down the mountainsides. Such continuous “ball-hooting,” as it was
called, gouged paths which rain and snow etched deeper into scars
of heavy erosion. Sometimes oxen and mules pulled, or “snaked,”
the timber through rough terrain to its flatcar destination. Horses
soon replaced the slower animals and proved especially adept at
“jayhooking,” or dragging logs down steep slopes by means of J-
hooks and grabs. When the logs gained speed and threatened to
overtake them, the men and nimble-footed horses simply stepped
onto a spur trail; the open link slipped off at the J-hook and the logs
slid on down the slope under their own momentum.
Even more ingenious skidding methods were devised. Splash-dams
of vertical hemlock boards created reservoirs on otherwise shallow,
narrow streams. The released reservoir, when combined with heavy
rains, could carry a large amount of timber far downstream. In the
mill pond, loggers with hobnailed boots kept the logs moving and
uncorked occasional jams. Another method devised to move virgin
timber down steep slopes was the trestled flume. The large, wooden
graded flumes provided a rapid but expensive mode of delivery. One
carried spruce off Clingmans Dome.
There were, finally, the loader and skidders. The railroad-mounted
steam loader was nicknamed the “Sarah Parker” after “a lady who
must have been real strong.” The skidder’s revolving drum pulled in
logs by spectacular overhead cables. Loaded with massive timber
lengths, these cables spanned valleys and retrieved logs from the
very mountaintops.
National Park Service
George Washington Shults and some neighbors
snake out large trunks with the help of six oxen.
Sometimes the lumber companies would hire such
local people to handle a specific part of the operation.
Today we call the process subcontracting.
Little River Lumber Company
Of the many kinds of trees logged in the Great
Smokies, the largest and most profitable were the
yellow-poplars, more commonly known as tulip trees.
A man could feel pretty small standing next to one of
them.
Little River Lumber Company
The great scale of the logging machinery was like
nothing the Smokies had seen before. Long trains
carried loads of huge tree trunks to sawmills after the
flat cars were loaded by railroad-mounted cranes.
To coordinate all of these operations efficiently required skill and
judgment. The lumber companies devised numerous approaches to
the problem of maximum production at lowest cost. They contracted
with individuals; Andy Huff, for example, continued to run a mill at
the mouth of Roaring Fork and paid his men a full 75 cents for a 16-
hour day. The corporations sometimes worked together; in one
maneuver, Little River helped Champion flume its spruce pulpwood
to the Little River railroad for shipment to Champion’s paper mill at
Canton, North Carolina. Haste and carelessness could lead to
shocking waste. When one company moved its operations during
World War I, 1.5 million board feet of newly cut timber was left to rot
at the head of Big Creek.
The ravages of logging led to fires. Although fires were sometimes
set on purpose to kill snakes and insects and to burn underbrush,
abnormal conditions invited abnormal mishaps. Parched soil no
longer held in place by a web of living roots, dry tops of trees piled
where they had been flung after trimming the logs, and flaming
sparks of locomotives or skidders: any combination of these caused
more than 20 disastrous fires in the Smokies during the 1920s. A
two-month series of fires devastated parts of Clingmans Dome,
Siler’s Bald, and Mt. Guyot. One holocaust on Forney Creek, ignited
by an engine spark, raced through the tops of 24-meter (80-foot)
hemlocks and surged over 5 kilometers (3 miles) in four hours. A site
of most intense destruction was in the Sawtooth range of the
Charlie’s Bunion area.
Despite the ravages of fire, erosion, and the voracious ax and saw,
all was not lost. Some two-thirds of the Great Smoky Mountains was
heavily logged or burned, but pockets of virgin timber remained in a
shrinking number of isolated spots and patches at the head of
Cataloochee, the head of Greenbrier, and much of Cosby and Deep
Creek. And as the 1920s passed into another decade, the vision of
saving what was left of this virgin forest, saving the land—saving the
homeland—grew in the lonely but insistent conscience of a small
number of concerned and convincing citizens.
 Conducting a preliminary survey of the park’s
boundaries in 1931 are (from left) Superintendent J.
Ross Eakin, Arthur P. Miller, Charles E. Peterson, O. G.
Taylor, and John Needham.
George A. Grant
 Birth of a Park
Logging dominated the life of the Great Smoky Mountains during the
early decades of the 20th century. But there was another side to that
life. Apart from the sawmills and the railroads and the general stores,
which were bustling harbingers of new ways a-coming, the higher
forests, the foot trails, and the moonshine stills remained as tokens
of old ways a-lingering. One person in particular came to know and
speak for this more primitive world.
Horace Kephart was born in 1862 in East Salem, Pennsylvania. His
Swiss ancestors were pioneers of the Pennsylvania frontier. During
his childhood, Kephart’s family moved to the Iowa prairie, where his
mother gave him a copy of the novel Robinson Crusoe by Daniel
Defoe. In the absence of playmates on the vast Midwest grassland,
young Kephart dreamed and invented his own games, fashioned his
own play swords and pistols out of wood and even built a cave out of
prairie sod and filled it with “booty” collected off the surrounding
countryside.
Horace Kephart never forgot his frontier beginnings. He saved his
copy of Robinson Crusoe and added others: The Wild Foods of
Great Britain, The Secrets of Polar Travel, Theodore Roosevelt’s The
Winning of the West. Camping and outdoor cooking, ballistics and
photography captured his attention and careful study.
Kephart polished his education with periods of learning and library
work at Boston University, Cornell, and Yale. In 1887 he married a
girl from Ithaca, New York, and began to raise a family. By 1890, he
was librarian of the well-known St. Louis Mercantile Library. In his
late thirties, Kephart grew into a quiet, intense loner, a shy and
reticent man with dark, piercing eyes. He remained an explorer at
heart, a pioneer, an individual secretly nurturing the hope of further
adventures.
Opportunity arrived in a strange disguise. Horace Kephart’s largely
unfulfilled visions of escape were combined with increasingly
prolonged periods of drinking. Experience with a tornado in the
streets of St. Louis affected his nerves. As he later recalled:
“... then came catastrophe; my health broke down. In the summer of
1904, finding that I must abandon professional work and city life, I
came to western North Carolina, looking for a big primitive forest
where I could build up strength anew and indulge my lifelong
fondness for hunting, fishing and exploring new ground.”
He chose the Great Smokies almost by accident. Using maps and a
compass while he rested at his father’s home in Dayton, Ohio, he
located the nearest wilderness and then determined the most remote
corner of that wilderness. After his recuperation he traveled to
Asheville, North Carolina, where he took a railroad line that wound
through a honeycomb of hills to the small way station of Dillsboro.
And from there, at the age of 42, he struck out, with a gun and a
fishing rod and three days’ rations, for the virgin mountainside forest.
After camping for a time on Dick’s Creek, his eventual wild
destination turned out to be a deserted log cabin on the Little Fork of
the Sugar Fork of Hazel Creek.
His nearest neighbors lived 3 kilometers (2 miles) away, in the
equally isolated settlement of Medlin. Medlin consisted of a post
office, a corn mill, two stores, four dwellings, and a nearby
schoolhouse that doubled as a church. The 42 households that
officially collected their mail at the Medlin Post Office inhabited an
area of 42 square kilometers (16 square miles). It was, as Kephart
describes it:
“... the forest primeval, where roamed some sparse herds of cattle,
razorback hogs and the wild beasts. Speckled trout were in all the
streams. Bears sometimes raided the fields and wildcats were a
common nuisance. Our settlement was a mere slash in the vast
woodland that encompassed it.”
But it was also, for Horace Kephart, a new and invigorating home.
He loved it. He thrived in it. At first he concentrated his senses on
the natural beauty around him, on the purple rhododendron, the
 flame azalea, the
fringed orchis, the
crystal clear
streams. Yet as the
months passed, he
found that he could
not overlook the
people.
The mountain
people were as
solidly a part of the
Smokies as the
boulders
themselves. These
residents of branch
and cove, of Medlin
and Proctor and all
the other tiny
settlements tucked
high along the
slanting creekbeds
of the Great Smoky
Mountains, these
distinctive “back of
beyond” hillside
farmers and work-
worn wives and
wary moonshine
George Masa distillers lodged in
Kephart’s
Horace Kephart, librarian-turned- consciousness and
mountaineer, won the hearts of the imagination with
Smokies people with his quiet and rock-like strength
unassuming ways. He played a and endurance.
major role in the initial movement
for a national park. Initially silent and
suspicious of this
stranger in their midst, families gradually came to accept him. They
approved of his quietness and his even-handed ways, even
confiding in him with a simple eloquence. One foot-weary distiller,
after leading Kephart over kilometers of rugged terrain, concluded:
“Everywhere you go, it’s climb, scramble, clamber down, and climb
again. You cain’t go nowheres in this country without climbin’ both
ways.” The head of a large family embracing children who spilled
forth from every corner of the cabin confessed: “We’re so poor, if free
silver was shipped in by the carload we couldn’t pay the freight.”
Kephart came to respect and to wonder at these neighbors who
combined a lack of formal education with a fullness of informal
ability. Like him, many of their personal characters blended a
weakness for liquor with a strong sense of individual etiquette. He
heard, for example, the story of an overnight visitor who laid his
loaded gun under his pillow; when he awoke the next morning, the
pistol was where he had left it, but the cartridges stood in a row on a
nearby table.
He met one George Brooks of Medlin: farmer, teamster, storekeeper,
veterinarian, magistrate, dentist. While Brooks did own a set of
toothpullers and wielded them mercilessly, some individuals
practiced the painful art of tooth-jumping to achieve the same result.
Uncle Neddy Carter even tried to jump one of his own teeth; he cut
around the gum, wedged a nail in, and made ready to strike the nail
with a hammer, but he missed the nail and mashed his nose instead.
None of these fascinating tales escaped the attention of Horace
Kephart. As he regained his health, the sustained energy of his
probing mind also returned. Keeping a detailed journal of his
experiences, he drove himself as he had done in the past. He
developed almost an obsession to record all that he learned, to know
this place and people completely, to stop time for an interval and
capture this mountain way of life in his mind and memory. For three
years he lived by the side of Hazel Creek. Though he later moved
down to Bryson City during the winters, he spent most of his
summers 13 kilometers (8 miles) up Deep Creek at an old cabin that
marked the original Bryson Place.
Kephart distilled much of what he learned into a series of books. The
Book of Camping and Woodcraft appeared in 1906 as one of the first
detailed guidebooks to woodsmanship, first aid, and the art we now
call “backpacking,” all based on his personal experience and
knowledge. There is even a chapter on tanning pelts. But the most
authoritative book concerned the people themselves. Our Southern
Highlanders, published in 1913 and revised nine years later, faithfully
retraces Kephart’s life among the Appalachian mountain folk after he
“left the tame West and came into this wild East.” And paramount
among the wilds of the East was the alluring saga of the moonshiner.

Laura Thornborough
Wiley Oakley, his wife, and children gather on the
porch of their Scratch Britches home at Cherokee
Orchard with “Minnehaha.” Oakley always said, “I
have two women: one I talk to and one who talks to
me.”
National Park Service
Oakley was a park guide before there was a park. And
in that role he nearly always wore a red plaid shirt. He
developed friendships with Henry Ford and John D.
Rockefeller and became known as the “Will Rogers of
the Smokies.”
In Horace Kephart’s own eyes, his greatest education came from the
spirited breed of mountain man known as “blockade runners” or
simply “blockaders.” These descendants of hard-drinking Scotsmen
and Irishmen had always liked to “still” a little corn whisky to drink
and, on occasion, to sell. But as the 1920s opened into the era of
Prohibition, the mountain distiller of a now contraband product
reached his heyday. He found and began to supply an expanding,
and increasingly thirsty market.
Stealth became the keynote in this flourishing industry. Mountaineers
searched out laurel-strangled hollows and streams that seemed
remote even to their keen eyes. There they assembled the copper
stills into which they poured a fermented concoction of cornmeal,
rye, and yeast known as “sour mash” or “beer.” By twice heating the
beer and condensing its vapors through a water-cooled “worm” or
spiral tube, they could approximate the uncolored liquor enjoyed at
the finest New York parties. And by defending themselves with
shotguns rather than with words, they could continue their
approximations.
In this uniquely romantic business, colorful characters abounded on
both sides of the law. Horace Kephart wrote about a particular pair of
men who represented the two legal extremes: the famous
moonshiner Aquilla Rose, and the equally resilient revenuer from the
Internal Revenue Service, W. W. Thomason.
Aquilla, or “Quill,” Rose lived for 25 years at the head of sparsely
populated Eagle Creek. After killing a man in self-defense and hiding
out in Texas awhile, Rose returned to the Smokies with his wife and
settled so far up Eagle Creek that he crowded the Tennessee-North
Carolina state line. Quill made whisky by the barrel and seemed to
drink it the same way, although he was occasionally seen playing his
fiddle or sitting on the porch with his long beard flowing and his
Winchester resting across his lap. His eleventh Commandment, to
“never get ketched,” was faithfully observed, and Quill Rose
remained one of the few mountain blockaders to successfully
combine a peaceable existence at home with a dangerous livelihood
up the creek.
W.W. Thomason visited Horace Kephart at Bryson City in 1919.
Kephart accepted this “sturdy, dark-eyed stranger” as simply a tourist
interested in the moonshining art. While Thomason professed
innocence, his real purpose in the Smokies was to destroy stills
which settlers were operating on Cherokee lands to evade the local
law. He prepared for the job by taking three days to carve and paint
a lifelike rattlesnake onto a thick sourwood club. During the following
weeks, he would startle many a moonshiner by thrusting the stick
close and twisting it closer.
When Kephart led the “Snake-Stick Man” into whiskyed coves in the
Sugarlands or above the Cherokee reservation, he found himself
deputized and a participant in the ensuing encounters. More often
than not, shots rang out above the secluded thickets. In one of these
shootouts, Thomason’s hatband, solidly woven out of hundreds of
strands of horsehair, saved this fearless revenuer’s life.