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Drug Addiction, Dysregulation of Reward, and Allostasis

Neuropsychopharmacology volume 24, pages 97129 (2001) | Download Citation

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Abstract

This paper reviews recent developments in the neurocircuitry and neurobiology of addiction from a perspective of allostasis. A model is proposed for brain changes that occur during the development of addiction that explain the persistent vulnerability to relapse long after drug-taking has ceased. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in the compulsive use and loss of control over drug-taking. The development of addiction recruits different sources of reinforcement, different neuroadaptive mechanisms, and different neurochemical changes to dysregulate the brain reward system. Counteradaptive processes such as opponent-process that are part of normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to form an allostatic state. Allostasis from the addiction perspective is defined as the process of maintaining apparent reward function stability by changes in brain reward mechanisms. The allostatic state represents a chronic deviation of reward set point and is fueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of this allostatic state as compulsive drug-taking and loss of control over drug-taking is hypothesized to be expressed through activation of brain circuits involved in compulsive behavior such as the cortico-striatal-thalamic loop. The view that addiction is the pathology that results from an allostatic mechanism using the circuits established for natural rewards provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and relapse.

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Acknowledgements

This is publication number 13306-NP from The Scripps Research Institute. GFK was supported by National Institutes of Health grants AA06420 and AA08459 from the National Institute on Alcohol Abuse and Alcoholism, DA04043 and DA04398 from the National Institute on Drug Abuse, and DK26741 from the National Institute of Diabetes and Digestive and Kidney Diseases. MLM was supported by Institut National de la Sante et de la Recherche Medicale, Universite de Bordeaux II, and Institut Universitaire de France. The authors would like to thank Drs. Barbara Mason, Bernard Carroll, Floyd Bloom, Markus Heilig, and Ms. Carrie Armel for their extremely helpful comments on the manuscript. The authors also would like to thank Mike Arends, Pat Brennan, and Isabelle Batby for their valuable assistance with manuscript preparation, and Janet Hightower for her tremendous help with the production of the illustrations.

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  1. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA

    • George F Koob
  2. Psychobiologie des Comportements Adaptatifs, INSERM, Unite 259, Universite de Bordeaux II, Bordeaux, France

    • Michel Le Moal

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https://doi.org/10.1016/S0893-133X(00)00195-0