title: Dopamine D2 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 D2 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 D2 receptors by 12% and 11%, respectively, when given for 14 days. Administration of the D2 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 D2 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 D2 receptor function to the efficacy of those drugs with potent effects on dopaminergic neuronal function.
authors.affiliation: Knoll Pharmaceuticals Research Department, Nottingham, UK.
authors.forename: K F
authors.initials: KF
authors.lastname: Martin
authors.forename: I
authors.initials: I
authors.lastname: Phillips
authors.forename: S C
authors.initials: SC
authors.lastname: Cheetham
authors.forename: D J
authors.initials: DJ
authors.lastname: Heal
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001667:Binding, Competitive / Q000187:drug effects; D018492:Dopamine Antagonists; D004565:Electroconvulsive Therapy; D006220:Haloperidol / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009627:Nomifensine / Q000493:pharmacokinetics / Q000494:pharmacology*; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012457:Salicylamides; D014191:Tranylcypromine / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D000928:Antidepressive Agents; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D009627:Nomifensine; D014191:Tranylcypromine; D020891:Raclopride; D006220:Haloperidol