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Forskolin promotes the development of ethanol tolerance in 6-hydroxydopamine-treated mice

Journal Article · · Life Sci.; (United States)
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 ..cap alpha../sub 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. 26 references, 2 figures.
Research Organization:
National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD
OSTI ID:
5589364
Journal Information:
Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 42:6; ISSN LIFSA
Country of Publication:
United States
Language:
English