Effect of treatment of rats with antidepressants on melatonin concentrations in the pineal gland and serum.

The effect of administration of antidepressant drugs to rats on catecholamine-induced rises in the concentration of melatonin in the pineal gland and serum was studied. Increases in melatonin levels were produced by either the exogenous administration of different doses of L-isoproterenol or by exposure of rats to darkness. Repeated administration of either desmethylimipramine or nialamide reduced significantly the elevation in melatonin concentrations in the pineal gland produced by either L-isoproterenol or darkness. The rise in serum melatonin seen at night was also blunted significantly in rats treated repeatedly with these drugs. By contrast, the concentration of melatonin in either the pineal gland or serum was not reduced in rats given desmethylimipramine or nialamide acutely. In fact, daytime concentrations of melatonin both in the gland and in serum were significantly increased after either acute or repeated treatment with nialamide. The nialamide-induced increase in daytime concentrations of melatonin in the pineal gland was prevented if the rats were treated with propranolol. The diminished hormonal responsiveness produced by the repeated administration of antidepressants occurred at a time when the binding of [3H]dihydroalprenolol to pineal gland homogenates was reduced. Thus, a hormonal response to catecholamines regulated via beta adrenergic receptor activation is reduced by repeated antidepressant treatments in conjunction with the development of beta adrenergic receptor subsensitivity.