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 ..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), Vol. 42:6
- Country of Publication:
- United States
- Language:
- English
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ETHANOL
TOXICITY
PHORBOL ESTERS
BIOLOGICAL EFFECTS
SYMPATHOMIMETICS
RECEPTORS
BIOCHEMICAL REACTION KINETICS
BRAIN
CYCLASES
DOPAMINE
MICE
NORADRENALINE
TOLERANCE
ADRENAL HORMONES
ALCOHOLS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARCINOGENS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
DRUGS
ENZYMES
ESTERS
HORMONES
HYDROXY COMPOUNDS
KINETICS
LYASES
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PROTEINS
REACTION KINETICS
RODENTS
STEROID HORMONES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology