PharmacologyBiochemistry& Behavior, Vol. 33, pp. 257-260. ©MaxwellPergamon Macmillanpie, 1989. Printed in the U.S.A. 0091-3057/89 $3.00 + .00 RAPID COMMUNICATION Patterns of Extracellular 5-Hydroxyindoleacetic Acid (5-HIAA) in the Paraventricular Hypothalamus (PVN): Relation to Circadian Rhythm and Deprivation-Induced Eating Behavior B. GLENN STANLEY,* DAVID H. SCHWARTZ,t LUIS HERNANDEZ,t SARAH F. LEIBOWITZ* AND BARTLEY G. HOEBELt *The Rockefeller University, 1230 York Avenue, New York, NY 10021 "~Princeton University, Department of Psychology, Princeton, NJ 08544 Received 2 December 1988 STANLEY, B. G., D. H. SCHWARTZ, L. HERNANDEZ, S. F. LEIBOWITZ AND B. G. HOEBEL. Patterns of extracellular 5-hydroxyindoleacetic acid (5-HIAA) in the paraventricular hypothalamus (PVN): Relation to circadian rhythm and deprivation- induced eating behavior. PHARMACOL BIOCHEM BEHAV 33(1) 257-260, 1989.--Daily rhythms in extracellular levels of the serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were examined in the region of the paraventricular nucleus (PVN), using intracerebral microdialysis combined with high performance liquid chromatography and electrochemical detection. Samples of PVN dialysate, from 11 rats on a 12/12 hr light/dark cycle, were collected and assayed for 5-1-1/AAevery 2 hr for 3 days. During the first 2 days the rats were given flee access to food. During the 3rd day they were deprived of food for a 24-hr period and then given food for 4 hr. The results showed that in freely-feeding rats, there was a 24-hr rhythm in the levels of 5-HIAA, with a marked transient peak just after the beginning of the dark portion of the light/dark cycle and stable levels at all other times. When the animals were food-deprived, PVN levels of this metabolite remained stable, and the early dark peak was abolished, suggesting that it might have been consequent to the eating behavior which normally occurred at this time. In the 4:hr refeeding period, there were no changes in 5-HIAA levels, despite the intense eating behavior which occurred during this time. These patterns of 5-HIAA in the PVN region, taken together with previous evidence, suggest that PVN serotonin metabolism may increase in association with feeding specifically in the early portion of the nocturnal eating period, when it may play a role in controlling food intake and macronutrient selection. Circadian rhythm Eating behavior Paraventricular nucleus Microdialysis Serotonin 5-Hydroxyindoleacetic acid CONVERGING evidence suggests that serotonergic neurons in- nervating the paraventricular nucleus (PVN) have a suppressive role in the control of eating behavior. Central administrations of serotonin (5-HT), or of drugs which release endogenous 5-HT, are most effective in the PVN (20,26), and conversely, electrolytic lesions of this nucleus are highly effective in attenuating the anorexia produced by peripheral injections of these drugs (25). A more specific function of PVN 5-ttT may be to suppress consump- tion of a particular macronutricnt, namely, carbohydrate. PVN injections of 5-HT or its agonists reduce ingestion of carbohydrate while having little or no effect on fat or protein intake (18, 20, 24). Most recently, this effect was found to vary in relation to the natural circadian cycle, with 5-HT exhibiting its greatest effec- tiveness at the start of the active (nocturnal) cycle (13, 20, 21, 24), a time when rats normally exhibit a preference for carbohydrate (22). This finding has been interpreted as reflecting a natural daily rhythm of serotonergic activity in the PVN. In a recent microdialysis study, primarily focused on daily rhythms of PVN NE (20), we also measured the serotonin metabolite 5-HIAA and observed results which may support this 257