tributed to many discoveries in neuroendocrinology and the neurobiology of stress including the discovery of opioid peptides and stress neurotransmitters, the neurochemical control of stress hormone, and reproductive hormone release. In addition, drug abuse research impacts on disciplines as diverse as molecular biology, the neurobiology of emotional behavior, and the neurobiology of cognitive function in the effort to understand the complex phenomena associated with a course of drug dependence.

The following chapter contains a technical overview illustrating the complexity of the neurotransmission processes involved in the neurobiology of drug dependence, a description of the many advances in understanding the neurobiological basis for drug dependence, a summary of gaps and needs, and finally recommendations for future research. The technical overview provides the vocabulary and basic concepts necessary to understand how drugs can interact at many different functional levels including the molecular, cellular, and systems levels. The section on accomplishments details the significant advances in understanding the neurobiology of drug reinforcement and the beginnings of our understanding of the processes of neuroadaptation to these systems associated with dependence. In addition, the chapter describes progress in human imaging research and the recent developments in understanding brain mechanisms of pain and analgesia. Gaps and needs are identified that focus on the chronic consequences of drug exposure in brain systems implicated in the motivational effects of drug dependence at the molecular, cellular, and system levels of analysis. Finally, the chapter identifies numerous areas for research opportunities that will aid in our understanding of the neurobiology of drug dependence and help integrate this basic research with the applied problems of vulnerability, treatment, and prevention of drug abuse. These areas include molecular neurobiology, genetics research, animal models of dependence, brain imaging, co-occurring psychiatric disorders, HIV models, neurotoxicity of drug dependence, immunology, analgesia and pain, and relapse and prolonged abstinence.


The human brain is composed of an enormous number of neurons, with estimates ranging from 10 billion to 10 trillion (reviewed by Kandel et al., 1991; Hyman and Nestler, 1993). These neurons are organized in such a way that they communicate with one another in a highly intricate and specific manner. This process of communication is referred to as synaptic transmission.

In a simplified scheme, neurons consist of a cell body or soma; mul-

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