J Neural Transm (1994) [Suppl] 41: 135-139 © Springer-Verlag 1994 Clorgyline effect on pineal melatonin biosynthesis in adrenalectomized rats pretreated with 6-hydroxydopamine S. Reuss', P. J . Requintina^, R. Riemann', and G . F . Oxenkrug^ ^Department of Anatomy, Johannes Gutenberg-University, Mainz, Federal Republic of Germany ^Pineal Research Laboratory, Department of Psychiatry and Human Behavior, Brown University, and Psychiatry Service, VAMC, Providence, Rhode Island, U.S.A. Summary. The response to administration of the specific monoamine oxidase A (MAO-A) blocker clorgyline was investigated in adult male Sprague-Dawley rats which were adrenalectomized four days prior to treatment or were additionally sympathectomized as newborns by injection of 6-hydroxydopamine. In both groups, the contents of pineal indoles melatonin and N-acetylserotonin were augmented, and the contents of 5- hydroxyindoleacetic acid and 5-hydroxyindoletryptophol decreased 90min following clorgyline injections when compared to rats receiving saline. The observed responses were less pronounced in rats both adrenalectomized and sympathectomized. The results are in line with the hypothesis that preservation from oxidation of both MAO-A substrates, noradrenahne and serotonin, upon clorgyline administration contributes to the observed increase in melatonin biosynthesis thought to be associated with the anti- depressant effects of M A O inhibition. Introduction Selective inhibition of monoamine oxidase-A type (MAO-A), but not of MAO-B, stimulates pineal melatonin (MEL) biosynthesis in rodents, primates and humans (Oxenkrug et al., 1984; for review see Oxenkrug, 1991). These findings might be of cHnical importance since selective M A O - A (but not MAO-B) inhibitors exert clinical antidepressive effects (Lipper et al., 1979). MEL synthesis is driven by postganghonic sympathetic fibres stemming from the superior cervical ganglia (SCG; Reuss and Moore, 1989). Removal of the SCG resulted in a loss of pineal MAO-A activity (Snyder et al., 1965). Experimental data suggest that the effect of MAO-A inhibitors might be mediated via stimulation of the physiological pathway of melatonin synthesis since ganglionectomy (Mclntyre et al., 1985) but not adrenal