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 alpha1-or beta adrenoceptor-mediated input on pinealocytes to these marked changes in melatonin production.
Similar content being viewed by others
References
Axelrod J (1974) The pineal gland: a neurochemical transducer. Science 184:1341
Axelrod J, Shein HM, Wurtman RJ (1969) Stimulation of C14-melatonin synthesis from C14-tryptophan by noradrenaline in rat pineal in organ culture. Proc Natl Acad Sci USA 62:544
Bade P, Rommelspacher H, Strauss S (1977) N-Acetyltransferase activity in pineal gland of rats treated with pargyline. Naunyn-Schmiedeberg's Arch Pharmacol 297:143
Beck-Friis JB, Kjellman BF, Aperia B (1985) Serum melatonin in relation to clinical variables in patients with major depressive disorder and a hypothesis of a low melatonin syndrome. Acta Psychiatr Scand 71:319
Brown R, Kocsis JH, Caroff S, Amsterdam J, Winokur A, Stokes PE, Frazer A (1985) Differences in nocturnal melatonin secretion between melancholic depressed patients and controls. Am J Psychiatry 142:811
Charney DS, Menkes DB, Heninger GR (1981) Receptor sensitivity and the mechanism of action of antidepressant treatment. Arch Gen Psychiatry 38:1160
Claustrat B, Chazot G, Brun J, Jordan D, Sassolas GA (1984) A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry 19(8):1215
Cohen RM, Ebstein RP, Daly JW, Murphy DL (1982) Chronic effects of a monoamine oxidase-inhibiting antidepressant: decreases in functional α-adrenergic autoreceptors precede the decrease in norepinephrine-stimulated cyclic adenosine 3′:5′-monophosphate systems in rat brain. J Neurosci: 2:1588
Cowen PJ, Fraser S, Sammons R, Green AR (1983) Atenolol reduces plasma melatonin concentration in man. Br J Clin Pharmacol 15:579
Friedman E, Yocca FD, Cooper TB (1984) Antidepressant drugs with varying pharmacological profiles alter rat pineal beta adrenergic-mediated function. J Pharmacol Exp Ther 228:545
Garrick NA, Tamarkin L, Taylor PL, Markey SP, Murphy DL (1983) Light and propranolol suppress the nocturnal elevation of serotonin in the cerebrospinal fluid of rhesus monkeys. Science 221:474
Garrick NA, Scheinin M, Chang W-H, Linnoila M, Murphy DL (1984) Differential effects of clorgyline on catecholamine and indoleamine metabolites in the cerebrospinal fluid of rhesus monkeys. Biochem Pharmacol 33:1423
Garrick NA, Tamarkin L, Murphy DL (1985) Marked enhancement of the nocturnal elevation of melatonin in rhesus monkeys by inhibition of monoamine oxidase (MAO) type A. The Pharmacologist 27:196 (Presented at American Society for Pharmacology and Experimental Therapeutics, Boston, Massachusetts, August, 1985)
Goridis C, Neff NH (1971) Evidence for a specific monoamine oxidase associated with sympathetic nerves. Neuropharmacology 10:557
Heydorn WE, Brunswick DJ, Frazer A (1982) Effect of treatment of rats with antidepressants on melatonin concentrations in the pineal gland and serum. J Pharmacol Exp Ther 222(3):534
Juillard MT, Collin JP (1980) Pools of serotonin in the pineal gland of the mouse: The mammalian pinealocyte as a component of the diffuse neuroendocrine system. Cell Tissue Res 213:273
King TS, Richardson BA, Reiter RJ (1982) Regulation of rat pineal melatonin synthesis: effect of monoamine oxidase inhibition. Mol Cell Endocrinol 25:327
Klein DC, Moore RY (1979) Pineal N-acetyltransferase and hydroxyindole-O-methyltransferase: control by the retinohypothalamic tract and suprachiasmatic nucleus. Brain Res 174:245
Klein DC, Rowe J (1970) Pineal gland in organ culture. Mol Pharmacol 6:164
Klein DC, Sugden D, Weller JL (1983) Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase. Proc Natl Acad Sci USA 80:599
Lewy AJ (1983) Biochemistry and regulation of mammalian melatonin production. In: Relkin R (ed) The pineal gland, Elsevier, New York, p 7
Mendlewicz J, Linkowski P, Branchey L, Weinberg U, Weitzman ED, Branchey M (1979) Abnormal 24 h pattern of melatonin secretion in depression. Lancet: 1362
Moyer JA, Greenberg LH, Frazer A, Weiss B (1981) Subsensitivity of the beta-adrenergic receptor-linked adenylate cyclase system of rat pineal gland following repeated treatment with desmethylimipramine and nialamide. Mol Pharmacol 19:187
Murphy DL, Campbell I, Costa JL (1978) The brain serotonergic system in the affective disorders. Prog Neuropsychopharmacol 2:1
Murphy DL, Lipper S, Pickar D, Jimerson D, Cohen RM, Garrick NA, Alterman IS, Campbell IC (1981a) Selective inhibition of monoamine oxidase type A: clinical antidepressant effects and metabolic changes in man. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors. The state of the art. Wiley, New York, p 189
Murphy DL, Pickar D, Jimerson D, Cohen RM, Garrick NA, Karoum F, Wyatt RJ (1981b) Biochemical indices of the effects of selective MAO inhibitors (clorgyline, pargyline and deprenyl) in man. In: Usdin E, Dahl S, Gram LF, Lingjaerde O (eds) Clinical pharmacology in psychiatry. MacMillan, London, p 307
Murphy DL, Garrick NA, Aulakh CS, Cohen RM (1984a) New contributions from basic science to understanding the effects of monoamine oxidase inhibiting antidepressants. J Clin Psychiatry 45:37
Murphy DL, Cohen RM, Garrick NA, Siever LJ, Campbell IC (1984b) Utilization of substrate selective monoamine oxidase inhibitors to explore neurotransmitter hypotheses of the affective disorders. In: Post RM, Ballenger JC (eds) Neurobiology of the mood disorders. Williams and Wilkins, Baltimore, p 587
Murphy DL, Tamarkin L, Sunderland T, Garrick NA, Cohen RM (1986) Human plasma melatonin is elevated during treatment with the monoamine oxidase inhibitors clorgyline and tranylcypromine but not deprenyl. Psychiatry Res 17:119
Murphy DL, Garrick NA, Tamarkin L, Taylor PL, Markey SP (1986) Effects of antidepressants and other psychotropic drugs on melatonin release and pineal gland function. J Neural Transm 21:291
Namboodiri MAA, Sugden D, Klein DC, Mefford IN (1983) 5-Hydroxytryptophan elevates serum melatonin. Science 221:659
Oxenkrug GF, McCauley R, McIntyre IM, Filipowicz C (1985) Selective inhibition of MAO-A but not MAO-B activity increases rat pineal melatonin. J Neural Transm 61:265
Parfitt A, Klein DC (1976) Sympathetic nerve endings in the pineal gland protect against acute stress-induced increase in N-acetyltransferase (E.C.2.3.1.5.) activity. Endocrinology 99:840
Parfitt A, Klein DC (1977) Increase caused by desmethylimipramine in the production of [3H]-melatonin by isolated pineal glands. Biochem Pharmacol 26:904
Reiter RJ (1980) The pineal gland and its hormones in the control of reproduction in mammals. Endocr Rev 1:109
Reppert SM, Perlow MJ, Tamarkin L, Klein DC (1979) A diurnal melatonin rhythm in primate cerebrospinal fluid. Endocrinology 104(2):295
Rollag MD, Niswender GD (1976) Radioimmunoassay of serum concentrations of melatonin in sheep exposed to different lighting regimens. Endocrinology 98(2):482
Sugden D, Aryan MA, Namboodiri A, Klein DC, Pierce JE, Grady R Jr, Mefford IN (1985) ovine pineal alpha1-adrenoceptors: Characterization and evidence for a functional role in the regulation of serum melatonin. Endocrinology 116:1960
Sugrue MF (1983) Chronic antidepressant therapy and associated changes in central monoaminergic receptor functioning. Pharmacol Ther 21:1
Sunderland T, Mueller EA, Cohen RM, Jimerson DC, Pickar D, Murphy DL (1985) Tyramine pressor sensitivity changes during deprenyl treatment. Psychopharmacology 86:432
Sunderland T, Tariot PN, Cohen RM, Newhouse PA, Mellow AM, Mueller EA, Murphy DL (1987) Dose-dependent effects of deprenyl on CSF monoamine metabolites in patients with Alzheimer's disease. Psychopharmacology 91:293
Tamarkin L, Craig CJ, Garrick NA, Wehr TA (1983) Effect of clorgyline (an MAO type A inhibitor) on locomotor activity in the Syrian hamster. Am J Physiol 245:R215
Tamarkin L, Baird CJ, Almeida OFX (1985) Melatonin: a coordinating signal for mammalian reproduction. Science 227:714
Vaughan GM (1986) Human melatonin in physiologic and diseased state: Neural control of the rhythm. J Neural Transm 21:199
Vetulani J, Sulser F (1975) Actions of various anti-depressant treatments reduces reactivity of noradrenergic cyclic AMP-generating system in limbic forebrain. Nature 257:495
Winer BJ (1971) Statistical Principles in experimental design. McGraw-Hill, New York
Wurtman RJ, Ozaki Y (1978) Physiological control of melantonin synthesis and secretion mechanisms generating rhythms in melatonin, methoxytryptophol and arginine vasotocin levels and effects on the pineal of endogenous catecholamines, the estrous cycle and environmental lighting. J Neural Transm [Suppl] 13:59
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Murphy, D.L., Garrick, N.A., Hill, J.L. et al. Marked enhancement by clorgyline of nocturnal and daytime melatonin release in rhesus monkeys. Psychopharmacology 92, 382–387 (1987). https://doi.org/10.1007/BF00210848
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00210848