Antidepressant drugs with varying pharmacological profiles alter rat pineal beta adrenergic-mediated function

Abstract

The effects of acute and chronic administrations of two antidepressant drugs with differing pharmacological profiles on pineal beta adrenergic receptor-mediated functions were examined in the rat. Animals were treated with control powdered food or with either imipramine or iprindole-containing diets (0.067%, w/w) for various time intervals. Animals were sacrificed during different phases of the light/dark cycle and pineal [3H]dihydroalprenolol (DHA) binding, N-acetyltransferase (NAT) activity, N-acetylserotonin (NAS) and melatonin levels were measured. Plasma drugs and metabolite concentrations were also assessed. A 3-day treatment with imipramine resulted in an unchanged pineal [3H] DHA binding and an increase in pineal serotonin (5-HT), NAS and melatonin. A comparable treatment with iprindole did not alter any pineal measures. Three weeks of imipramine treatment resulted in therapeutic plasma drug and metabolite concentrations and elicited a reduction (31%) in the density of pineal [3H] DHA binding. This treatment, in addition, suppressed the dark-induced activation of the intracellular enzyme NAT (38%) and the concentrations of NAS (25%) and melatonin (23%) without altering pineal 5-HT rhythm. No apparent shift was observed in the NAT, NAS and melatonin rhythms. Chronic treatment with the atypical antidepressant iprindole for 3 weeks resulted in-plasma iprindole concentrations of 76 ng/ml and a significant reduction (24%) in pineal 5-HT levels 5 hr into the dark phase of the light/dark cycle. Pineal NAT activity and NAS and melatonin content were not significantly reduced by this treatment. However, 4 weeks of iprindole ingestion produced plasma drug concentrations of 141 ng/ml and significantly reduced pineal [3H] DHA binding density (18%) without changing binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)