Orexin A modulates food intake and the hypothalamo-pituitary-adrenal axis function through different hypothalamic mechanisms

MORENO G; PERELLO M; GAILLARD RC; SPINEDI E

Napoli, Italia

Congreso; 11 European NeuroEndocrine Association; 2004

ENEA

Orexin A belongs to the endogenous hypothalamic orexigenic (OXG) neuropeptides family. Although Orexin A is able to stimulate the hypothalamo-pituitary-adrenal (HPA) axis function, the intrinsic mechanisms involved in this effect are still of controversy. In the present study we confirm that Orexin A does centrally stimulate HPA axis function in the normal conscious rat. In addition we attempted to determine whether the central effects of Orexin A on both energy metabolism and HPA axis function are dependent of an intact NPY-ergic system. For this purpose, adult, ad libitum fed or food-restricted female rats with normal (CTR) and lesioned-hypothalamus, due to neonatal monosodium L-glutamate (MSG) treatment, were studied after i.c.v. administration of Orexin A. The effectiveness of Orexin A treatment was monitored by changes in both HPA axis function and 3 hour-food intake. The results indicated that hypophagic MSG-lesioned rats, bearing decreased hypothalamic NPY expression, contrary to CTR rats, did not respond to Orexin A-induced food intake. In contrast, i.c.v. Orexin A administration was able to stimulate the HPA axis in both experimental groups, the response being even more pronounced in MSG than in CTR rats. Our data support that the hypothalamic orexigenic effect of Orexin A seems to be fully dependent of intact NPY-ergic activity, in contrast to the Orexin A-induced HPA axis response, which is independent of this NPY activity. Thus, our study strongly suggests that the main hypothalamic site of action of Orexin A, in its ability to increase HPA axis function, is probably the paraventricular rather than the arcuate nucleus.     (Supported by PICT 5191/99 and FNSR 32-064107.00)