Dopamine D 2 receptors: A potential pharmacological target for nomifensine and tranylcypromine but not other antidepressant treatments

Abstract

Treatment for 1 or 14 days by IP injection with the antidepressants, amitriptyline (10 mg/ kg), bupropion (30 mg/kg), desipramine (10 mg/kg), GBR 12909 (10 mg/kg), sibutramine HCl (3 mg/kg), mianserin (5 mg/ kg), and zimeldine (10 mg/kg), did not affect the number or affinity of dopamine D 2 receptors determined by [ 3H]raclopride binding to rat striatal membranes. Similarly, neither did a single, nor repeated (five times over 10 days), electroconvulsive shock, given under halothane anaesthesia, have any effect on [ 3H]raclopride binding parameters. By contrast, the noradrenaline and dopamine reuptake inhibitor, nomifensine (5 mg/kg), and the monoamine oxidase inhibitor, tranylcypromine (5 mg/ kg), decreased the number of dopamine D 2 receptors by 12% and 11%, respectively, when given for 14 days. Administration of the D 2 receptor antagonist, haloperidol (1 mg/kg), for 14 days increased the number of [ 3H]raclopride binding sites by 17%. Thus, the data demonstrate that although nomifensine and tranylcypromine decrease D 2 receptor number after 14 days administration, this adaptive change is not observed with other antidepressant treatments. However, the findings do not preclude a contribution of altered dopamine D 2 receptor function to the efficacy of those drugs with potent effects on dopaminergic neuronal function.