Drug addiction, dysregulation of reward, and allostasis

This paper reviews recent developments in the neurocircuitry and neurobiolo gy of addiction from a perspective of allostasis. A model is proposed for b rain changes that occur during the development of addiction that explain th e persistent vulnerability to relapse long after drug-taking has ceased. Ad diction 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 dif ferent sources of reinforcement, different neuroadaptive mechanisms, and di fferent neurochemical changes to dysregulate the brain reward system. Count eradaptive processes such as opponent-process that are part of normal homeo static limitation of reward function fail to return within the normal homeo static range and are hypothesized to form an allostatic state. Allostasis f rom the addiction perspective is defined as the process of maintaining appa rent reward function stability by changes in brain reward mechanisms. The a llostatic state represents a chronic deviation of reward set point and is f ueled not only by dysregulation of reward circuits per se, but also by the activation of brain and hormonal stress responses. The manifestation of thi s 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 rea listic approach to identifying the neurobiological factors that produce vul nerability to addiction and relapse. [Neuropsychopharmacology 24:97-129, 20 02] (C) 2000 American College of Neuropsychopharmacology. Published by Else vier Science Inc.