Ethanol differentially enhances adrenocortical response in LS and SS mice.

The stimulatory effect of ethanol on the hypothalamo-pituitary-adrenal (HPA) axis was investigated in the long-sleep (LS) and short-sleep (SS) lines of mice. Plasma corticosterone concentrations peaked 30 min after IP administration of ethanol in both lines of mice. Ethanol produced dose-dependent elevations in plasma corticosterone in both LS and SS mice; however, at low doses of ethanol (0.25 to 1 g/kg) the adrenocortical response observed in LS mice was markedly greater than in SS mice. Passive immunoneutralization of circulating corticotropin releasing factor (CRF) completely abolished ethanol-induced elevation in plasma corticosterone in LS mice. CRF or ACTH (adrenocorticotropin) produced dose-dependent elevations in plasma corticosterone in the two lines of mice. Epinephrine co-administered with CRF did not potentiate the adrenocortical response obtained with CRF in either line of mice, and hexamethonium only slightly attenuated ethanol-induced elevations in plasma corticosterone in both lines of mice, suggesting that differentially elevated plasma catecholamines are not responsible for differences in ethanol-induced adrenocortical response. The results suggest that differential adrenocortical response to ethanol exhibited by LS and SS mice is due primarily to differential ethanol-induced CRF release.