Ethanol modulates corticotropin releasing hormone release from the rat hypothalamus: does acetaldehyde play a role?
METHODS
Ethanol (EtOH) activates hypothalamic-pituitary-adrenal (HPA) axis, resulting in adrenocorticotropin hormone, glucocorticoid release, and in modifications of the response of the axis to other stressors. The initial site of EtOH action within the HPA system seems to be the hypothalamus. Thus, to determine the mechanisms responsible for these effects, we investigated: (i) whether EtOH was able to release corticotrophic releasing hormone (CRH) from incubated hypothalamic explants; (ii) whether acetaldehyde (ACD), its first metabolite formed in the brain by catalase activity, might play a role in EtOH activity. To this aim, rat hypothalamic explants were incubated with: (i) medium containing EtOH at 32.6 x 10(3) microM; (ii) different concentration of ACD (1, 3, 10, and 30 microM); (iii) EtOH plus 3amino-1,2,4-triazole (3AT, 32 x 10(3) microM) an inhibitor of cerebral catalase; (iv) ACD plus D-penicillamine (DP, 50.3 x 10(3) microM) an ACD-trapping agent. CRH levels were evaluated by a radioimmunoassay.


RESULTS
Incubation with EtOH induced a 7-fold increase in CRH secretion, with respect to basal levels; ACD was able to stimulate CRH release in a dose-dependent manner; the inhibition of cerebral catalase by 3AT blocked EtOH-induced CRH outflow; the inactivation of ACD by DP reverted the ACD-stimulating effect on CRH secretion.


CONCLUSIONS
These data show that both EtOH and acetaldehyde are able to increase hypothalamic CRH release from the rat hypothalamus and that acetaldehyde itself appears to be the mediator of EtOH activity.
Cannizzaro
Carla
C
Department of Pharmacological Sciences P. Benigno, University of Palermo, Palermo, Italy. carlacannizzaro@unipa.it
La Barbera
Marco
M
Plescia
Fulvio
F
Cacace
Silvana
S
Tringali
Giuseppe
G
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D003346:Corticotropin-Releasing Hormone; D000079:Acetaldehyde