A key role for corticotropin-releasing factor in alcohol dependence.
Recent data indicate that alcohol dependence induces long-term neuroadaptations that recruit a negative emotional state. This leads to excessive alcohol ingestion motivated by relief of negative emotionality. A key mechanism in this transition to negative reinforcement is a recruitment of corticotropin-releasing factor (CRF) signaling within the amygdala. Long term upregulation of CRF(1) receptors is observed in the amygdala following a history of dependence, and CRF antagonists selectively block emotionality, excessive alcohol drinking and stress-induced reinstatement of alcohol-seeking in post-dependent animals. Innate upregulation of CRF(1) receptor expression mimics the post-dependent phenotype, both with regard to emotional responses and ethanol self-administration. Therefore, the CRF system is emerging as a key element of the neuroadaptive changes driving alcoholism and as a major target for its treatment.
Heilig
Markus
M
Laboratory of Clinical and Translational Studies, National Institute of Alcohol Abuse and Alcoholism (NIAAA), NIH, 10 Center Dr., 1/5334, Bethesda, MD 20892, USA. markus.heilig@mail.nih.gov
Koob
George F
GF
D000222:Adaptation, Physiological / Q000187:drug effects; D000339:Affect / Q000187:drug effects / Q000502:physiology*; D019973:Alcohol-Related Disorders / Q000378:metabolism*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D016739:Behavior, Addictive / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D012201:Reward
D000431:Ethanol; D003346:Corticotropin-Releasing Hormone