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lüll A key role for corticotropin-releasing factor in alcohol dependence Heilig M; Koob GFTrends Neurosci 2007[Aug]; 30 (8): 399-406Recent 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.|Adaptation, Physiological/drug effects[MESH]|Affect/drug effects/*physiology[MESH]|Alcohol-Related Disorders/*metabolism[MESH]|Amygdala/*metabolism[MESH]|Animals[MESH]|Behavior, Addictive/*metabolism[MESH]|Corticotropin-Releasing Hormone/*metabolism[MESH]|Ethanol/pharmacology[MESH]|Humans[MESH]|Reward[MESH] |