title: Modification of dopamine receptor-mediated processes after chronic ethanol intoxication: a possible mechanism.
abstract: Animals undergoing withdrawal from chronic ethanol treatment displayed significantly impaired function of dopaminergic systems in the CNS. Autonomic and behavioral response to dopaminergic agonists were reduced, as was the stimulation by dopamine of dopamine-sensitive adenylate cyclase from the striatal region of brain. In addition, the ability of neuroleptics to stimulate tryosine hydroxylase activity in the subcortex was diminished. These findings suggested a decreased sensitivity of dopaminergic receptors during ethanol withdrawal, and in time course of appearance and disappearance, the decreased sensitivity appeared to parallel ethanol withdrawal hyper-excitability. Moreover, the responsiveness of dopamine-sensitive adenylate cyclase could be restored by in vitro exposure to physiologically attainable concentrations of ethanol, suggesting that this system had become dependent on the presence of ethanol for normal function. The mechanism of the decreased sensitivity, in particular for the adenylate cyclase, but perhaps also for other dopamine receptor-mediated processesx, may be inefficient coupling between receptor and enzyme, as a result of changes in neuronal membrane structure produced by chronic exposure to ethanol and withdrawal.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome
chemical_list: D011954:Receptors, Dopamine; D000431:Ethanol; D000262:Adenylyl Cyclases; D004298:Dopamine