Reduced hypothalamic POMC and anterior pituitary CRF1 receptor mRNA levelsafter acute, but not chronic, daily "binge" intragastric alcohol administration

Background: Endogenous corticotropin-releasing factor (CRF), its pituitary CRF, receptor, and proopiomelanocortin (POMC) may be involved in the hypoth alamic-pituitary-adrenal (HPA) responses to alcohol. Methods: Alcohol (1.5 g/kg) or water was administered intragastrically to m ale Fischer rats after the "binge" pattern regimen, that is, three times da ily at 1 hr intervals at the beginning of the light cycle. The levels of CR F, CRF, receptor, and POMC mRNAs in the hypothalamic-pituitary axis were me asured after acute (1 day) or chronic (14 days) binge pattern alcohol admin istration. Plasma levels of ACTH and corticosterone were measured to examin e time-dependent alterations of HPA responses. Results: Plasma ACTH and corticosterone levels were elevated dramatically a fter I day of acute binge pattern alcohol administration. After 14 days of chronic alcohol, however, no elevation in plasma ACTH levels and an attenua ted elevation in plasma corticosterone levers were found. CRF mRNA levels i n the hypothalamus were not altered after either acute or chronic alcohol a dministration. CRF, receptor mRNA revels in the anterior pituitary were dec reased significantly after acute administration, with no change after chron ic alcohol administration. POMC mRNA levels in the anterior pituitary were not altered by either acute or chronic alcohol administration. In the hypot halamus, POMC mRNA levels were decreased significantly after acute but not chronic binge alcohol administration. Conclusions: These results suggest that (1) rats exposed to chronic binge a lcohol develop tolerance in HPA activity, as shown by no elevation of ACTH and an attenuated corticosterone response to chronic alcohol after initial dramatic elevations by acute alcohol administration; (2) a concurrent acute decrease in CRF, receptor mRNA levels in the anterior pituitary is associa ted with increased HPA activity, and (3) alterations of POMC gene expressio n in the hypothalamic region may have implications for a molecular understa nding of the neuroendocrine response to alcohol.