Drug Abuse: Hedonic Homeostatic Dysregulation

Author:

Koob George F.12,Moal Michel Le12

Affiliation:

1. G. F. Koob is at The Scripps Research Institute, Department of Neuropharmacology CVN-7, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

2. M. Le Moal is at the University of Bordeaux II, INSERM, Unite 259, rue Camille Saint-Saens, Bordeaux, Cedex 33077, France.

Abstract

Understanding the neurobiological mechanisms of addiction requires an integration of basic neuroscience with social psychology, experimental psychology, and psychiatry. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug-taking. Sensitization and counteradaptation are hypothesized to contribute to this hedonic homeostatic dysregulation, and the neurobiological mechanisms involved, such as the mesolimbic dopamine system, opioid peptidergic systems, and brain and hormonal stress systems, are beginning to be characterized. This framework provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and to relapse in individuals with a history of addiction.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference101 articles.

1. J. H. Jaffe in Goodman and Gilman's The Pharmacological Basis of Therapeutics A. G. Gilman T. W. Rall A. S. Nies P. Taylor Eds. (Pergamon New York ed. 8 1990) pp. 522–573.

2. World Health Organization International Statistical Classification of Diseases and Related Health Problems (World Health Organization Geneva 10th revision 1990).

3. Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association Washington DC ed. 4 1994).

4. A recent Institute of Medicine report [Institute of Medicine Pathways of Addiction (National Academy Press Washington DC 1996)] used a three-stage conceptualization of drug-taking behavior that applies to all psychoactive drugs whether licit or illicit: use abuse and dependence. “Use” of drugs is the taking of drugs in the narrow sense to distinguish it from a more intensified pattern of use. “Abuse” refers to any harmful use regardless of whether the behavior constitutes a disorder in the DSM-IV of the American Psychiatric Association. “Dependence” refers to “substance dependence” as defined by DSM-IV or “addiction” as defined by International Classification of Diseases (ICD 10).

5. Koob G. F., Nestler E. J., J. Neuropsychiatry Clin. Neurosci. 9, 482 (1997);

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