Marked enhancement by clorgyline of nocturnal and daytime melatonin release in rhesus monkeys

Abstract

The type A monoamine oxidase (MAO)-inhibiting antidepressant clorgyline (1 mg/kg/24 days) administered to rhesus monkeys increased night-time cerebrospinal fluid (CSF) melatonin concentrations 3-fold and day-time maltonin values 5-fold. Other circadian parameters of melatonin release, including the peak time and duration of nocturnal melatonin elevation measured during continuous CSF collection periods of 90 min duration over 24-h cycles, were unaffected by clorgyline. While pinealocytes are thought to contain only MAO-B, treatment with the selective MAO-B inhibitor deprenyl (2 mg/kg/24 days) did not alter day or night-time melatonin concentrations. These results are consistent with MAO-A and non-selective MAO inhibitors acting via blockade of degradation of the preferential substrates of MAO-A, serotonin and/or norepinephrine, in adrenergic neurons entering the pineal gland. Further study is needed to evaluate the relative contributions of an increased availability of the melatonin precursor, serotonin, or a sustained net increase in alpha 1-or beta adrenoceptor-mediated input on pinealocytes to these marked changes in melatonin production.