Neurobiology of Addiction
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《新英格兰医药杂志》
The front cover of this book includes a reproduction of Pablo Picasso's The Absinthe Drinker — an appropriate beginning to a compelling work that spans the spectrum from molecules to the mind and behavior. In the painting, a middle-aged woman sits at a table, her upper body tightly bound by her right arm, which crosses her body in a contorted fashion and restrains her left arm. Her right hand, disproportionately large as compared with the rest of her body, seems to hold her back from reaching out for a glistening bottle and a waiting glass placed on the table before her. Deep in thought, her mouth taut, while the position of her left hand puts her in a pose reminiscent of Auguste Rodin's The Thinker, she appears intense, perhaps even sad, as she contemplates the bottle and glass. I believe that this portrait of profound human anguish and ambivalence encapsulates the essence of the book it introduces to the reader — desire intermixed with, and in intense conflict with, insurmountable and out-of-control suffering — specifically, the human condition of addiction. How can addicts, who on the surface may appear like the rest of us, continue to reach for that bottle, all the while knowing that when they are intoxicated their actions shame themselves, hurt those they love, and destroy their bodies and their souls?
(Figure)
The Absinthe Drinker by Pablo Picasso, 1901.
From the Bridgeman Art Library. ? 2006 Estate of Pablo Picasso/Artists Right Society (ARS), New York.
George Koob and Michel Le Moal, world-renowned behavioral pharmacologists and neuroscientists, aim to reveal the neurobiologic underpinnings of addiction by disassembling this complex human disease process into fundamental components, using as tools a rich variety of laboratory models. It is indeed fortunate for readers that the authors do not stop at "a thorough review of the extant body of research on the neurobiology of addiction" (as the publisher describes the book on its back cover) but also make use of their decades of experience as active laboratory researchers to " diverse findings on the neurobiology of addiction to provide a heuristic framework for future work" (also from the back cover). Their insights are particularly timely and useful for those engaged in translational investigations of this enormous, worldwide problem, which in the United States alone consumes well over $500 billion per year in health care and other human costs.
The backbone of the book is a detailed review of the world literature concerning the neurobiology of addiction to psychostimulants, opioids, alcohol, nicotine, and cannabinoids. Each agent is examined from multiple perspectives — namely, the relevant neurocircuitry involved and the various cellular and molecular levels of analyses. Competent, comprehensive, and extensively referenced, the book is clearly appropriate for researchers in the field. However, what sets it apart from other books, in my opinion, are the synthetic chapters, which constitute a remarkably cogent introduction to addiction, a detailed general discussion of animal models of addiction, thoughtful descriptions of competing neurobiologic theories of addiction, and a translational chapter in which recent findings on neuroimaging are considered and linked to the more fundamental concepts previously used to examine the neurocircuitry of addiction. To pique the interest of basic scientists and to underscore the importance of addiction to humankind, the appendixes provide a compendium of literary and scientific descriptions of human experiences with addiction to each of the drugs discussed in the text.
The pièce de résistance of the book is a scholarly treatise on the pathophysiological underpinnings of addiction — the transition from "normal" drug use (for example, drinking a glass of wine with a fine evening meal) to compulsive and self-destructive patterns of self-administration (staying drunk instead of going to work, and overlooking one's own needs as well as those of one's loved ones) — from the perspective of adaptive changes in the brain's reward and stress systems.
The term "allostasis" is proposed as the most applicable to this process, in contradistinction to the more familiar principles of homeostasis, which have guided much of physiology and medicine in the past century. Allostasis, it is argued, allows the organism flexibility, matching coping strategies to the changing demands of the environment, to continually reset the nervous system's set points in anticipation of demand. Within the contemporary context of chronic diseases, such brain regulatory processes are proposed as more relevant than homeostasis. Although the concept of allostasis is put forward in this book as leading logically, progressively, and irrevocably to the behavioral abnormality of addiction, most physicians will recognize that the proposed model is equally relevant to many of the chronic diseases we must face in the 21st century, wherein the actions of multiple organ systems are orchestrated by the nervous system.
Peter R. Martin, M.D.
Vanderbilt University Medical School
Nashville, TN 37232
peter.martin@vanderbilt.edu(By George F. Koob and Mic)
(Figure)
The Absinthe Drinker by Pablo Picasso, 1901.
From the Bridgeman Art Library. ? 2006 Estate of Pablo Picasso/Artists Right Society (ARS), New York.
George Koob and Michel Le Moal, world-renowned behavioral pharmacologists and neuroscientists, aim to reveal the neurobiologic underpinnings of addiction by disassembling this complex human disease process into fundamental components, using as tools a rich variety of laboratory models. It is indeed fortunate for readers that the authors do not stop at "a thorough review of the extant body of research on the neurobiology of addiction" (as the publisher describes the book on its back cover) but also make use of their decades of experience as active laboratory researchers to " diverse findings on the neurobiology of addiction to provide a heuristic framework for future work" (also from the back cover). Their insights are particularly timely and useful for those engaged in translational investigations of this enormous, worldwide problem, which in the United States alone consumes well over $500 billion per year in health care and other human costs.
The backbone of the book is a detailed review of the world literature concerning the neurobiology of addiction to psychostimulants, opioids, alcohol, nicotine, and cannabinoids. Each agent is examined from multiple perspectives — namely, the relevant neurocircuitry involved and the various cellular and molecular levels of analyses. Competent, comprehensive, and extensively referenced, the book is clearly appropriate for researchers in the field. However, what sets it apart from other books, in my opinion, are the synthetic chapters, which constitute a remarkably cogent introduction to addiction, a detailed general discussion of animal models of addiction, thoughtful descriptions of competing neurobiologic theories of addiction, and a translational chapter in which recent findings on neuroimaging are considered and linked to the more fundamental concepts previously used to examine the neurocircuitry of addiction. To pique the interest of basic scientists and to underscore the importance of addiction to humankind, the appendixes provide a compendium of literary and scientific descriptions of human experiences with addiction to each of the drugs discussed in the text.
The pièce de résistance of the book is a scholarly treatise on the pathophysiological underpinnings of addiction — the transition from "normal" drug use (for example, drinking a glass of wine with a fine evening meal) to compulsive and self-destructive patterns of self-administration (staying drunk instead of going to work, and overlooking one's own needs as well as those of one's loved ones) — from the perspective of adaptive changes in the brain's reward and stress systems.
The term "allostasis" is proposed as the most applicable to this process, in contradistinction to the more familiar principles of homeostasis, which have guided much of physiology and medicine in the past century. Allostasis, it is argued, allows the organism flexibility, matching coping strategies to the changing demands of the environment, to continually reset the nervous system's set points in anticipation of demand. Within the contemporary context of chronic diseases, such brain regulatory processes are proposed as more relevant than homeostasis. Although the concept of allostasis is put forward in this book as leading logically, progressively, and irrevocably to the behavioral abnormality of addiction, most physicians will recognize that the proposed model is equally relevant to many of the chronic diseases we must face in the 21st century, wherein the actions of multiple organ systems are orchestrated by the nervous system.
Peter R. Martin, M.D.
Vanderbilt University Medical School
Nashville, TN 37232
peter.martin@vanderbilt.edu(By George F. Koob and Mic)