Timmons & Hamilton: Drugs, Brains & Behavior Drugs, Brains and Behavior by C. Robin Timmons & Leonard W. Hamilton About the Authors Related Materials TABLE OF CONTENTS Chapter 1: Behavior and the Chemistry of The Brain Chapter 2: General Methods of Brain/Behavior Analysis Chapter 3: Psychopharmacological Concepts Chapter 4: Specific Fears, Vague Anxieties And The Autonomic Nervous System Chapter 5: Pain and Other Stressors Chapter 6: Depression and the Reward System Chapter 7: Schizophrenia as a Model of Dopamine Dysfunction Chapter 8: General Arousal Chapter 9: Tolerance, Drug Abuse And Habitual Behaviors Definitions References List of Figures The Making of Drugs, Brains and Behavior Available on the web both at Rutgers University and at Drew University. Also available on diskette. http://www.users.drew.edu/ctimmons/drugs/INDEX.HTML (1 of 2) [9/8/2001 10:15:09 AM] Timmons & Hamilton: Drugs, Brains & Behavior Comments and Questions may be emailed to either [email protected] or [email protected] Notice Much of this work was previously published by Prentice Hall as Principles of Behavioral Pharmacology. The copyrights have been assigned to the authors, C. Robin Timmons and Leonard W. Hamilton. This electronic version may be freely copied and distributed for educational and non-profit purposes with this message and full attribution to the authors. http://www.users.drew.edu/ctimmons/drugs/INDEX.HTML (2 of 2) [9/8/2001 10:15:09 AM] Timmons & Hamilton: Drugs, Brains and Behavior -- Ch 1 Chapter 1 BEHAVIOR AND THE CHEMISTRY OF THE BRAIN A. HISTORICAL DEVELOPMENTS Preamble Folk Remedies The Unveiling of Chemical Transmission B. THE SYNAPSE AND CHEMICAL TRANSMISSION Basic Principles Major Features of Chemical Transmission C. THE ORGANIZATION AND LOGIC OF CHEMICAL CODING The Autonomic Nervous System as a Model Receptor Sites Chemical Coding of Brain Functions D. INTERACTIONS OF BEHAVIOR, ENVIRONMENT AND BRAIN CHEMISTRY http://www.users.drew.edu/ctimmons/drugs/chap01.htm (1 of 21) [9/8/2001 10:15:36 AM] Timmons & Hamilton: Drugs, Brains and Behavior -- Ch 1 Convergence of Disciplines Dynamics of Brain Chemistry and Behavior E. SUMMARY Principles Terms Click here to return to main Table of Contents BEHAVIOR AND THE CHEMISTRY OF THE BRAIN A. HISTORICAL DEVELOPMENTS Preamble The birthplace of humanity will be marked not by bones, but by behavior. This is not to belittle the importance of bones; the fossil record will continue to sharpen the focus of our geographic and temporal origins. However, the defining characteristic of Homo sapiens is not the thumb and not the brain case, rather, it is the workings of the brain, the behaviors, the feelings, the mind (if you will). The interpretation of the geological record goes well beyond physical structure. The skull may be found in proximity to various tools, the bones of animals (perhaps with damage that matches tool structure), plant remains, evidence of households, and so forth. All of this can lead to an educated guess about the culture and behavior of our ancestors. A guess about the function of the brain. Indeed, it is no accident that the term skull is frequently replaced by the term brain case, suggesting that the missing contents are more important than the empty skull. We agree. The purpose of this brief excursion into our ancestry is to provide an extreme example of an old philosophical issue, the mind-body problem (cf., Utall, 1978). Is the mind or behavior of humans a product of the body or is it a separate (spiritual) entity? Nearly all of us are willing to sit on both sides of this philosophical fence: http://www.users.drew.edu/ctimmons/drugs/chap01.htm (2 of 21) [9/8/2001 10:15:36 AM] Timmons & Hamilton: Drugs, Brains and Behavior -- Ch 1 On the one hand, we are easily convinced that brain cases tell us something about the nature of the contents. Although it is hard to imagine anything less dynamic than a million year old skull ensconced in stone, we believe that this evidence can provide at least a global clue about behavior potential. The surrounding artifacts (tools, etc.) supplement this evidence and enrich our interpretation of the culture of our ancestors. Paradoxically, as the evidence gets stronger, our beliefs tend to get weaker. Moving forward in time to our current existence, we have no difficulty accepting the fact that serious brain damage leads to serious changes in behavior. The brain is obviously the organ of (abnormal) behavior. The brain may be recognized as the organ of behavior, but each of us tenaciously hangs onto the belief that we are more than the product of our brain physiology. There is a strong sensation that we have an individual identity (self) and a free will which allows us to control our own brain. Students of the brain and behavior are not immune to these feelings, but the feelings must be suspended on occasion to pursue the fundamental belief that behavior has predictable causes, and that these causes may be found in the workings of the brain. The purpose of this text is to provide a better understanding of the vehicle for the feelings, emotions, and motivations of the human experience. We will attempt to develop an understanding of the interpenetration of brain, behavior, and environment. We will discuss the chemistry of behavior in both the literal sense of neurochemistry and the figurative sense of an analysis of the reactions with the environment. Perhaps a word of reassurance is needed concerning the level of analysis that will be pursued. There are three traditional and overlapping subdivisions of the material covered in this textbook: Neurochemistry is the study of the chemical reactions and functions of the individual neuron or small populations of neurons. Behavioral Pharmacology is the analysis of the effects of drugs on behavior (usually of animals), with particular emphasis on the development and classification of drugs. Psychopharmacology is the study of the effects of drugs on behavior (usually of humans), with particular emphasis on changes in mood, emotions, and psychomotor abilities. Each of these subdisciplines is reductionistic in its own way and tends to analyze the brain and/or behavior in a manner that seems sterile to most beginning students. We do not intend to reduce behavior and chemistry to the simplest level in the way that a chemist would analyze a compound. Indeed, our goal is to synthesize rather than analyze. We intend to further your appreciation by increasing the awareness of the mechanisms of behavior. Connoisseurs of wine are knowledgeable about climate, grapes, and fermentation; they are no less appreciative because they know the vintner's craft. Aficionados of classical music are knowledgeable about tone, rhythm and structure; they are no less appreciative http://www.users.drew.edu/ctimmons/drugs/chap01.htm (3 of 21) [9/8/2001 10:15:36 AM] Timmons & Hamilton: Drugs, Brains and Behavior -- Ch 1 because they know the score. Our goal is to enrich your appreciation of behavior by explaining some of the processes that underlie your feelings. Enough preambling. Let us trace some of the historical events in both the field and the laboratory that have helped to shape our current conceptualizations of the chemical bases of behavior. Folk Remedies The roots of behavioral pharmacology (no pun intended) go back many centuries. A working knowledge of drug use clearly antedates the knowledge that the brain is the organ of behavior, and probably antedates the appearance of the first medical practitioners. In fact, it seems likely that medical practitioners arose as a result of the accumulating knowledge about folk remedies. Those individuals who were especially knowledgeable about the remedies of their culture probably became the medical practitioners. The history of specific drugs will be incorporated in many of the later chapters, but a few examples at this point will provide the flavor of both the power and the complexity of folk medicine. (Several of the specific histories that follow, and numerous additional ones, are presented in more detail in the various editions of Gilman, Goodman & Gilman; e.g., 1980.) The old adage that one man's cure is another man's poison seems particularly relevant to the history of pharmacology. Many of the compounds that are useful in medicine are derived from arrow poisons, ordeal poisons (to detect practitioners of witchcraft), and pesticides. A particularly good example of such multiple applications is the use of atropine by the ancient Hindus and Romans. This compound, an extract of the nightshade and related plants, was used as a tool by the professional poisoners of the Middle Ages. At the same time, fashionable women were placing drops of atropine solution into their eyes as a cosmetic. The dilation of the pupils made the women more appealing by causing males to believe they were the object of emotional attraction. These antithetical uses led Linne' to name the shrub Atropos belladonna (Atropos, after one of the three fates, who cut the thread of life; belladonna means beautiful woman.) Today, men and women alike have drops of atropine placed in their eyes, but primarily for the purpose of eye examinations. It is also used for a wide range of medicinal purposes and, as we will see throughout the text, continues to be widely used as a research tool. An extract from the foxglove plant (Digitalis purpura--the flower looks like a purple finger) was used in an equally diverse fashion. The ancient Romans used digitalis as a tonic, a rat poison, a diuretic, an emetic, an arrow poison and an ordeal poison. More recently, it has been used by more modern physicians for the treatment of dropsy (a vaguely defined anemic disorder) and various disorders of the heart muscle.