CHANGES IN SEROTONIN LEVEL AND TURNOVER IN DISCRETE HYPOTHALAMIC NUCLEI AFTER PINEALECTOMY AND MELATONIN ADMINISTRATION TO RATS

The influence of the pineal gland on the hypothalamic serotonergic fun ction was examined by studying the effects of long-term pinealectomy ( 1 month) and melatonin replacement (500 mu g/kg; 10 days) on serotonin (5-HT.) and 5-hydroxyindoleacetic acid (5-HIAA) content as well as on the in vivo 5-HT synthesis rate in discrete hypothalamic nuclei. Pine alectomy was followed by a significant decrease of 5-HT content in the anterior hypothalamic nuclei (AHN) and the ventromedial hypothalamic nuclei (VMHN), and also in 5-HIAA content in lateral (LPON) and medial preoptic nuclei (MPON). The 5-HT synthesis rate, estimated from the a ccumulation of 5-hydroxytryptophan after blockade of the l-amino acid decarboxylase activity, were also decreased in the AHN and the paraven tricular hypothalamic nuclei (PVHN) of pinealectomized rats. In contra st, an enhanced 5-HT synthesis rate and basal 5-HIAA content were foun d in the suprachiasmatic nuclei (SCN) after pinealectomy. Daily treatm ent with melatonin for 10 days reversed most of the effects induced by pinealectomy. Thus, melatonin increased the levels of 5-HT in the AHN and VMHN, and slightly increased the 5-HIAA content in preoptic nucle i. In addition, melatonin increased the 5-HT synthesis rate in the AHN and VMHN, but also in the MPON, VMHN and dorsomedial hypothalamic nuc lei (DMHN) where pinealectomy had no effect. By contrast, melatonin tr eatment did not affect SCN 5-HT synthesis rate, although it decreased 5-HIAA levels. The results demonstrate that melatonin is able to stimu late 5-HT metabolism in most of the hypothalamic areas, but inhibits S CN 5-HT function. Some of the effects of melatonin seems to be exerted by modulating the synthesis of the amine, although melatonin likely a lso interacts with other regulatory processes of 5-HT function (i.e. r elease/uptake). The well defined presence of melatonin receptors in th e rat SCN, and its absence in other hypothalamic structures, suggest t hat this may be the mechanism mediating the differential response to e ndogenous melatonin. Moreover, the larger effect of exogenous melatoni n in relation to pinealectomy suggests the presence of melatonin unesp ecific effects possibly owing to supraphysiological doses. The present findings may be relevant for the mode of action of melatonin and its implication in several endocrine and behavioral functions mediated by serotonergic neurons. Copyright (C) 1996 Elsevier Science Ltd