Down-regulation of cerebral beta-adrenoceptors induced by long term administration of antidepressants is prevented by ethanol.
Treatment with desipramine (20 mg/kg/d i.p.) for 21 days induces down-regulation of beta-adrenergic receptors and reduces receptor-mediated stimulation of the adenylate cyclase suggesting homologous desensitization. Chronic treatment with ethanol (2.5 g/kg/d and 5 g/kg/d p.o.) diminishes functionality of the signal transduction at various levels in a dose-dependent manner without changes in the number of beta-adrenergic receptors suggesting heterologous desensitization. Combined treatment prevents receptor down-regulation whereas stimulation of the receptor-coupled adenylate cyclase system remains diminished. The results are discussed with respect to possible mechanisms by which ethanol exerts the effects as disturbance of receptor-Ns protein coupling and/or inhibition of protein kinases.
Rommelspacher
H
H
Dept. of Neuropsychopharmacology, Free University, Berlin, F.R. Germany.
Strauss
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D001921:Brain / Q000187:drug effects*; D003891:Desipramine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000493:pharmacokinetics; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D004082:Dihydroalprenolol; D000262:Adenylyl Cyclases; D003891:Desipramine