Allostasis and addiction: Role of the dopamine and corticotropin-releasing factor systems

Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic function, is defined as the process of achieving stability through physiological or behavioral change. Two types of biological processes have been proposed to describe the mechanisms underlying allostasis in drug addiction, a within-system adaptation and a between-system adaptation. In the within-system process, the drug elicits an opposing, neutralizing reaction within the same system in which the drug elicits its primary and unconditioned reinforcing actions, while in the between-system process, different neurobiological systems that the one initially activated by the drug are recruited. In this review, we will focus our interest on alterations in the dopaminergic and corticotropin releasing factor systems as within-system and between-system neuroadaptations respectively, that underlie the opponent process to drugs of abuse. We hypothesize that repeated compromised activity in the dopaminergic system and sustained activation of the CRF–CRF1R system with withdrawal episodes may lead to an allostatic load contributing significantly to the transition to drug addiction.

► The opponent process theory postulates that drugs trigger two opposing motivational process. ► The a-process has fast onset and offset and the b-process is opposite, slower to start and last longer. ► Decreased dopaminergic function in the NAC and CeA mediate the habituation of the a-process. ► Activation of the CRF systems in the CeA and VTA mediates the increase in b-process in dependent subjects. ► Interaction between the dopamine and CRF systems may represent the opponent-process mechanisms of drug withdrawal.