Development of functional dependence on ethanol in dopaminergic systems.
Withdrawal of mice from chronic ethanol treatment results in a decreased responsiveness of striatal (but not mesolimbic) dopamine-sensitive adenylate cyclase activity to stimulation by dopamine. This subsensitivity is not apparent at the time of withdrawal from chronic feeding of ethanol, when animals are still intoxicated, but becomes evident as ethanol is eliminated from the animals. Addition of ethanol in vitro to tissue homogenates from ethanol-withdrawn animals, at concentrations similar to those found in brain at the time of withdrawal, normalizes the response of the adenylate cyclase to dopamine. No difference is evident between control and ethanol-withdrawn animals in stimulation of adenylate cyclase by sodium fluoride. The specificity of the response of striatal adenylate cyclase to stimulation by dopamine, as compared to other transmitters, is unaltered by chronic ethanol feeding. Chronic treatment with ethanol and withdrawal also does not affect the specific binding of spiroperidol in either striatal or mesolimbic regions. It is suggested that the decreased response of adenylate cyclase to dopamine in ethanol-withdrawn animals results from decreased efficiency of coupling between dopamine "receptor" sites and catalytic units of adenylate cyclase.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000437:Alcoholism / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004361:Drug Tolerance; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008032:Limbic System / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013134:Spiperone / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D013997:Time Factors
D000431:Ethanol; D013134:Spiperone; D000262:Adenylyl Cyclases; D004298:Dopamine