Ethanol is able to activate the hypothalamic-pituitary-adrenal (HPA) axis, and to modify its response to other stressors, releasing adrenocorticotropic hormone (ACTH), and glucocorticoid release, (Lee et al 1999, 2000). In the brain ethanol is diverted by catalase activity into acetaldehyde, which is reported to mediate some of its behavioural and neurochemical effects. (Peana et al 2008, Melis et al 2007) Thus, to clarifìy the mechanisms underlying ethanol activity on the HPA axis we investigated :1) ethanol effect on CRH release from incubated hypothalamic explants; 2) the role of acetaldehyde (ACD), in mediating ethanol activity. To this aim, rat hypothalamic explants were incubated with: 1) medium containing ethanol at 150 mg %; 2) different concentrations of ACD (4.4I, 13.2II, 44III, 132IV 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 significant increase in CRH secretion (p< 0.01); ACD was able to increase CRH release in a dose dependent manner (I=p<0.05; II-IV=p<0.005 ); the inhibition of cerebral catalase by 3-AT blocked ethanol-induced CRH outflow (p<0.01); the inactivation of ACD by D-P reverted 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.
|Numero di pagine||1|
|Stato di pubblicazione||Published - 2009|