Down-regulation of rat beta-adrenoceptors by clenbuterol or desipramine does not require chronic treatment: [H-3]CGP-12177 binding reveals rapid (24 hour) modulation

Desipramine (DMI, 15 mg/kg, s.c.) decreased [H-3]CGP-12177-labelled cortical beta-adrenoceptor density (B-max) by 30% upon chronic (14 day) treatment, However, even a single dose (in mg/kg) of DMI (15) or the beta-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of beta-adrenoceptor B-max (-15%; p < 0.01), Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [H-3]CGP-12177-labelled beta-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the B-max of [H-3]ketanserin-labelled 5-HT2A receptors on acute treatment. These results show that beta-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.