Allostatic mechanisms have been hypothesized to be involved in maintaining a functioning brain reward system that has relevance for the pathology of addiction (Koob and Le Moal 2001). Two components are hypothesized to adjust to challenges of the brain produced by drugs of abuse: underactivation of brain reward transmitters and circuits and recruitment of the brain anti-reward or brain stress systems (Fig. 4). Thus, the very physiological mechanism that allows rapid responses to environmental challenge becomes the source of pathology if adequate time or resources are not available to shut off the response (one example is the interaction between CRF and norepinephrine in the brainstem and basal forebrain that could lead to pathological anxiety; Koob 1999).
