Upregulation of Voluntary Alcohol Intake, Behavioral Sensitivity to Stress, and Amygdala Crhr1 Expression Following a History of Dependence
Biological Psychiatry Article in Press, Corrected Proof 21 June 2007

A history of alcohol dependence recruits increased voluntary alcohol intake and sensitivity to stress. Corticotropin-releasing hormone (CRH) has been implicated in this transition, but underlying molecular mechanisms remain unclear.

Alcohol drinking was upregulated long-term following a history of dependence. Fear suppression of behavior was selectively potentiated in postdependent animals. This persisted 3 months after alcohol exposure and was reversed by the selective CRH-R1 antagonist 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) (10 mg/kg).

Forced swim stress increased alcohol intake in postdependent animals but not in control animals. Behavioral changes were paralleled by an upregulation of Crhr1 transcript expression within basolateral (BLA) and medial (MeA) amygdala and Crh messenger RNA (mRNA) in central amygdala (CeA). In contrast, Crhr2 expression was down in the BLA.

Neuroadaptations encompassing amygdala CRH signaling contribute to the behavioral phenotype of postdependent animals.

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Reprint Request E-Mail: markus.heilig@mail.nih.gov
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