Down-regulation of beta-adrenoceptors in rat cortex by repeated administration of desipramine, electroconvulsive shock and clenbuterol requires 5-HT neurones but not 5-HT.

Repeated administration to rats of desipramine (5 mg kg-1, twice daily for 14 days), clenbuterol (5 mg kg-1, twice daily for 14 days) or electroconvulsive shocks (5 ECS over 10 days) decreased the number of beta-adrenoceptors in the cortex. Injection of 5,7-dihydroxytryptamine into the lateral ventricle produced a selective depletion of cerebral 5-HT, particularly in the cortex. In confirmation of earlier studies, this lesion prevented the decrease in the number of beta-adrenoceptors produced by desipramine. However, it was found that this lesion also prevented the down-regulation of beta-adrenoceptors produced by repeated electroconvulsive shock and administration of clenbuterol. Treatment of rats with p-chlorophenylalanine (PCPA) produced a similar depletion of cerebral content of 5-HT. However, this depletion did not prevent the decrease in density of beta-adrenoceptors induced by desipramine or electroconvulsive shock. It is concluded that the modulation of the decrease in the number of beta-adrenoceptors by diverse antidepressant treatments is not by the action of 5-HT itself, but by the action of some other factor present at 5-HT terminals, which is removed by a neurotoxic lesion.