FUNCTIONAL IMPAIRMENT OF HYPOTHALAMIC CORTICOTROPIN-RELEASING FACTOR NEURONS WITH IMMUNOTARGETED TOXINS ENHANCES FOOD-INTAKE INDUCED BY NEUROPEPTIDE-Y

Previous work has shown that administration of corticotropin-releasing factor (CRF) into the lateral ventricle antagonizes the orexigenic ef fect of neuropeptide Y (NPY), and central injection of CRF antagonist, alpha-helical CRF(9-41) enhanced NPY-induced food intake in satiated rats. The aim of the present study was to determine the effects of sel ective inactivation of hypothalamic CRF neurons on food intake induced by NPY injection and to delineate which hypothalamic nucleus is invol ved in this NPY/CRF interaction related to the regulation of food inta ke. Impairment of CRF neuron function by immunotargeting of a ricin A chain toxin with a monoclonal antibody to CRF (CRF-MAb) has been previ ously reported. Administration of CRF-MAb/toxins into the paraventricu lar nucleus (PVN) two weeks prior to testing produced markedly enhance d eating induced by injection of NPY into the same nucleus. This effec t was accompanied by a 60% decrease in CRF content within the hypothal amus and a 43% decrease of CRF in the median eminence, a site of proje ction of CRF neurons from the PVN. In contrast, injection of CRF-MAb/t oxins into the ventromedial nucleus of the hypothalamus (VMH) did not modify the feeding induced by NPY injection into this hypothalamic are a. Systemic pretreatment with the synthetic glucocorticoid dexamethaso ne at a dose known to downregulate the levels of CRF in the PVN also e nhanced the feeding induced by intra-PVN injection of NPY. This sugges ts that an equilibrium between CRF and NPY neuronal function within th e PVN may play an important role in the regulation of food intake. Thi s interactive mechanism may provide some partial explanation of the ea ting disorders related to stress, in particular anorexia nervosa.