Ethanol activates hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenocorticotropic hormone (ACTH) glucocorticoid release, and a modification of the response of this axis to other stressors (Lee et al 1999, 2000). To determine the mechanisms responsible for these effects we investigated : 1) whether ethanol was able to release CRH from incubated hypothalamic explants; 2) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in ethanol effects. To this aim, rat hypothalamic explants were incubated with: 1) medium containing ethanol at 150 mg %; 2) different concentrations of ACD (4.4, 13.2, 44, 132 x 10-3 mg%); 3) ethanol plus 3-amino-1,2,4-triazole (3-AT, 269 mg%), an inhibitor of cerebral catalase; 4) ACD plus D-penicillamine (D-P, 74.6 mg%), an ACD-trapping agent. CRH levels were evaluated by a radioimmunoassay. Our results show that: incubation with ethanol (150 mg %) induced a seven-fold increase in CRH secretion (p< 0.01); ACD was able to increase CRH release in a dose dependent manner (p<0.05; p<0.005); the inhibition of cerebral catalase by 3-AT blocked the ethanol-induced CRH outflow (p<0.01); the inactivation of ACD by D-P reverted the ACD-stimulating effect on CRH secretion (p<0.05). These data show that both ethanol and ACD are able to increase hypothalamic CRH release, and that ACD itself appears to be the mediator of ethanol activity.
|Number of pages||1|
|Publication status||Published - 2009|