The effect of psychoactive drugs on beta-adrenergic receptor binding sites in rat brain

The effect of a variety of psychotropic drugs, given to rats repeatedly over 16 days, on the number of beta-adrenergic receptor binding sites in cerebral cortex was measured. Labelled dihydroalprenolol, [³H]-DHA, was used to measure beta-adrenergic binding sites. Both tricyclic antidepressants (amitriptyline, chlorimipramine, desmethylimipramine and nortriptyline) and monoamine oxidase inhibitors (nialamide and tranylcypromine) lowered [³H]-DHA binding significantly. Repeated treatment of rats with the antidepressant. iprindole. produced the same effect as did treatment with bupropion. However, the experimental antidepressant mianserin did not reduce [³H]-DHA binding nor did 11 other psychoactive compounds including chlorpromazine, diazepam, l-DOPA, tripelennamine and cocaine. The reduction in [³H]-DHA binding produced by nialamide or iprindole treatment was due to a reduction in the maximum number of beta-adrenergic receptor binding sites. Drug treatment-induced lowering of [³H]-DHA binding sites in cerebral cortex appears to have utility as a pre-clinical test for antidepressant drugs.