Corticotropin-releasing factor in the paraventricular nucleus modulates feeding induced by neuropeptide Y.
Central administration of neuropeptide Y (NPY) exerts a potent orexigenic effect in rats, whereas injection of corticotropin-releasing factor (CRF) suppresses food intake. Anatomical evidence of NPY-containing terminals located in close proximity to CRF-containing neurons and terminals of the hypothalamus and amygdala suggests possible interactions of these neuropeptide systems in food-intake regulation. The present study examined the effect of local administration of the CRF antagonist, alpha-helical CRF9-41, or peripheral treatment with dexamethasone on NPY-induced hyperphagia. Injection of a 250-ng dose of alpha-hel CRF within the paraventricular nucleus (PVN) of the hypothalamus significantly potentiated the feeding induced by a 500-ng dose of NPY injected into the same locus. In contrast, feeding induced by administration of the 500-ng dose of NPY into the ventromedial hypothalamus (VMH) was not modified by intra-VMH pre-treatment with a 250-ng dose of CRF antagonist. No effects of NPY or alpha-hel CRF on feeding were observed after administration into the central nucleus of the amygdala. Systemic pre-treatment with the synthetic glucocorticoid dexamethasone at a dose known to downregulate the function of CRF neurons in the PVN (100 micrograms/kg) enhanced feeding induced by intra-PVN administration of a 500-ng dose of NPY. These results suggest that hypothalamic CRF systems in the PVN exert inhibitory control over NPY-induced food intake.
Scripps Research Institute, Department of Neuropharmacology, La Jolla, CA 92037.
S C
SC
Heinrichs
F
F
Menzaghi
E M
EM
Pich
R L
RL
Hauger
G F
GF
Koob
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects / Q000502:physiology*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology*; D010913:Pituitary-Adrenal System / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D009478:Neuropeptide Y; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone