The effect of chronic antidepressant administration on beta-adrenoceptor function of the rat pineal.

Abstract

1 The beta-adrenoceptor agonist, isoprenaline (1.5-3.0 mg kg(-1) intravenously), produced a dose-related increase in rat pineal melatonin content. This increase was prevented by pretreatment with the selective beta(1)-adrenoceptor antagonist, atenolol (2 mg kg(-1)), but not by the beta(2)-adrenoceptor antagonist, butoxamine (2 mg kg(-1)). The beta(2)-adrenoceptor agonist, terbutaline (5.0 mg kg(-1)), produced a moderate increase in pineal melatonin content.2 Repeated daily administration of desmethylimipramine (10 mg kg(-1) for 10 days) and maprotiline (10 mg kg(-1) for 10 days), antidepressants predominantly inhibiting noradrenaline (NA) uptake, reduced the isoprenaline-induced increase in pineal melatonin content. Amitriptyline (20 mg kg(-1) for 14 days), a drug which inhibits both NA and 5-hydroxytryptamine (5-HT) uptake, had a similar effect. The beta-adrenoceptor agonist, clenbuterol (5 mg kg(-1) for 14 days), also attenuated the increase in pineal melatonin produced by isoprenaline.3 In contrast, chronic administration of the selective 5-HT uptake inhibitor, fluoxetine (10 mg kg(-1) for 10 days), or the antidepressants, iprindole and mianserin (both 20 mg kg(-1) for 14 days), which do not inhibit monoamine uptake, failed to reduce the increase in pineal melatonin following isoprenaline. Repeated electroconvulsive shock was similarly without effect.4 Ten hours after the final dose of desmethylimipramine (10 mg kg(-1)) once daily for 10 days there was no change in the usual dark phase increase in pineal melatonin.5 The data suggest that repeated administration of certain antidepressant drugs results in reduced pineal beta-adrenoceptor sensitivity. However the lack of change in the dark phase increase in pineal melatonin following repeated desmethylimipramine, implies that the reduced ss-adrenoceptor sensitivity may be part of an adaptive process which maintains normal pineal function. Therefore the decrease in beta-adrenoceptor number in the brain reported after chronic antidepressant administration may not be associated with a change in overall synaptic function.