Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient

Corticotropin releasing hormone (CRH) acts on the central nervous system to alter energy balance and influence both food intake and sympathetically-me diated thermogenesis. CRH is also reported to inhibit food intake in severa l models of hyperphagia including neuropeptide Y (NPY)-induced eating. The recently identified CRH-related peptide, urocortin (UCN), also binds with h igh affinity to CRH receptor subtypes and decreases food intake in food-dep rived and non-deprived rats. The present experiment characterized further t he feeding and metabolic effects of UCN by examining its impact after direc t injections into the paraventricular nucleus (PVN) of the hypothalamus. In feeding tests (n=8), UCN (50-200 pmol) was injected into the PVN at the on set of the dark cycle and food intake was measured 1, 2 and 4 h postinjecti on. In separate rats (n=8), the metabolic effects of UCN were monitored usi ng an open circuit calorimeter which measured oxygen consumption (V-O2) and carbon dioxide production (Vco,). Respiratory quotient (RQ) was calculated as V-CO2/V-O2. UCN suppressed feeding at all times studied and reliably de creased RQ within 30 min of infusion. Additional work examined the effect o f UCN (150-100 pmol) pretreatment on the feeding and metabolic effects of N PY NPY, injected at the start of the dark period, reliably increased 2 h fo od intake. This effect was blocked by PVN UCN administration, Similarly, UC N blocked the increase in RQ elicited by NPY alone. These results suggest t hat UCN-sensitive mechanisms within the PVN may modulate food intake and en ergy substrate utilization, possibly through an interaction with hypothalam ic NPY (C) 2001 Elsevier Science B.V. All rights reserved.