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 effect 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 selective inactivation of hypothalamic CRF neurons on food intake induced by NPY injection and to delineate which hypothalamic nucleus is involved in this NPY/CRF interaction related to the regulation of food intake. Impairment of CRF neuron function by immunotargeting of a ricin A chain toxin with a monoclonal antibody to CRF (CRF-MAb) has been previously reported. Administration of CRF-MAb/toxins into the paraventricular nucleus (PVN) two weeks prior to testing produced markedly enhanced eating induced by injection of NPY into the same nucleus. This effect was accompanied by a 60% decrease in CRF content within the hypothalamus and a 43% decrease of CRF in the median eminence, a site of projection of CRF neurons from the PVN. In contrast, injection of CRF-MAb/toxins into the ventromedial nucleus of the hypothalamus (VMH) did not modify the feeding induced by NPY injection into this hypothalamic area. Systemic pretreatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the levels of CRF in the PVN also enhanced the feeding induced by intra-PVN injection of NPY. This suggests that an equilibrium between CRF and NPY neuronal function within the PVN may play an important role in the regulation of food intake. This interactive mechanism may provide some partial explanation of the eating disorders related to stress, in particular anorexia nervosa.
Menzaghi
F
F
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
Heinrichs
S C
SC
Pich
E M
EM
Tilders
F J
FJ
Koob
G F
GF
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000032:analysis / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D004435:Eating / Q000187:drug effects*; D007033:Hypothalamus, Middle / Q000166:cytology / Q000187:drug effects*; D000922:Immunotoxins / Q000494:pharmacology*; D007267:Injections; D008297:Male; D009474:Neurons / Q000737:chemistry / Q000502:physiology*; D009478:Neuropeptide Y / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus; D051381:Rats; D017208:Rats, Wistar
D000922:Immunotoxins; D009478:Neuropeptide Y; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone