Forskolin promotes the development of ethanol tolerance in 6-hydroxydopamine-treated mice.
Partial depletion of brain norepinephrine by 6-hydroxydopamine prevents the development of functional tolerance to ethanol in mice. This blockade of tolerance development was overcome by daily intracerebroventricular injections of forskolin. These results suggest that interaction of norepinephrine with post-synaptic beta-adrenergic receptors, and activation of adenylate cyclase, is important for the development of ethanol tolerance. Interaction of norepinephrine with alpha 1-adrenergic receptors may be less crucial, since treatment with a phorbol ester activator of protein kinase C did not restore the development of tolerance in mice treated with 6-hydroxydopamine. The importance of the beta-adrenergic receptor-coupled adenylate cyclase system for development of ethanol tolerance, in addition to its previously-reported role in long-term potentiation, suggests that this system may influence neuroadaptive processes in general.
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000008:administration & dosage / Q000494:pharmacology*; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000633:toxicity*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016627:Oxidopamine; D012016:Reference Values
D006892:Hydroxydopamines; D005576:Colforsin; D000431:Ethanol; D016627:Oxidopamine