The bed nucleus is a neuroanatomical substrate for the anorectic effect of corticotropin-releasing factor and for its reversal by nociceptin/orphanin FQ.
Nociceptin/orphanin FQ (N/OFQ), the endogenous ligand of the opioid N/OFQ receptor (NOP), possesses marked functional anti-stress and anti-corticotropin-releasing factor (CRF) actions. We have shown that intracerebroventricular injection of N/OFQ reverses the hypophagic effect induced by stress or by CRF given intracerebroventricularly. To shed new light on the mechanisms involved in the anti-CRF action of N/OFQ, we investigated the ability of N/OFQ to prevent CRF-induced anorexia after microinjection studies into brain areas of potential interest in the control of feeding behavior and coexpressing NOP and CRF receptors. These areas include the bed nucleus of the stria terminalis (BNST), the central amygdala (CeA), the locus ceruleus (LC), the ventromedial hypothalamus (VMH), the paraventricular nucleus (PVN), and the dorsal raphe (DR). The results demonstrated that the anorectic effect of 0.04 nmol of CRF per rat (200 ng per rat) given intracerebroventricularly is reversed by pretreatment with 0.01-0.21 nmol of N/OFQ per rat (25-500 ng per rat) injected into the BNST but not into the CeA, LC, VMH, PVN, or DR. Microinjection of 0.01-0.02 nmol of CRF per site (50-100 ng per site) into the BNST but not into the CeA or the LC induced marked anorexia in food-deprived rats. Pretreatment with 0.01-0.21 nmol of N/OFQ per site (25-500 ng per site) into the BNST also blocked the anorectic action of 0.02 nmol of CRF per site (100 ng per site) given in the same area. Finally, intra-BNST microinjection of 0.01-0.21 nmol of N/OFQ per site (25-500 ng per site) did not modify food intake in either food-sated or food-deprived rats. These data demonstrate that the BNST is involved in the modulation of CRF-induced anorexia, which is prevented by activation of N/OFQ receptors.
Ciccocioppo
Roberto
R
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, 62032 Camerino, Italy. roberto.ciccocioppo@unicam.it
Fedeli
Amalia
A
Economidou
Daina
D
Policani
Federica
F
Weiss
Friedbert
F
Massi
Maurizio
M
D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000855:Anorexia / Q000139:chemically induced / Q000188:drug therapy*; D001067:Appetite Depressants / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D004333:Drug Administration Routes; D004435:Eating / Q000187:drug effects; D008125:Locus Coeruleus / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D018847:Opioid Peptides / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012686:Septal Nuclei / Q000187:drug effects* / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D000097629:Nociceptin
D001067:Appetite Depressants; D003346:Corticotropin-Releasing Hormone; D018847:Opioid Peptides; D000097629:Nociceptin