The role of corticotropin-releasing factor in drug addiction

The goal of this article is to summarize available data examining the physi ological significance of brain corticotropin-releasing factor (CRF) systems in mediating the behavioral and physiological effects of several classes o f abused drugs, including opioid and psychostimulant drugs, alcohol and sed ative hypnotics, nicotine, and cannabinoids. An initial discussion of CRF n eurobiology is followed by consideration of the role of CRF in drug-induced activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, the be havioral effects of drugs (e.g., locomotor activity, anxiogenic-like respon ses), drug self-administration, drug withdrawal, and relapse to drug-seekin g. Subsequently, neurochemical changes in brain CRF in response to acute an d chronic drug exposure are examined. A major conclusion derived hom the da ta reviewed is that extrahypothalamic brain CRF systems are critically invo lved in behavioral and physiological manifestations of drug withdrawal and in relapse to drug-taking behavior induced by environmental stressors. On t he other hand, it appears that hypothalamic CRF, via its action on the HPA axis, is involved in the reinforcing effects of cocaine and alcohol, and th e locomotor activating effects of psychostimulant drugs. These preclinical data may provide a rationale for the development of CRF-based pharmacothera pies for the treatment of compulsive drug use in humans.