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.