neuropeptide-y and beta-funaltrexamine

Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) are opioid peptides which are selective partial agonists of μ-opioid receptor. We studied the effects of EM-2 injected into the arcuate nucleus (ARC) of the hypothalamus on feeding behavior and gene expression of orexigenic [agouti-related peptide (AgRP), neuropeptide Y (NPY) and orexin-A] and anorexigenic [cocaine and amphetamine-regulated transcript (CART), corticotrophin releasing hormone (CRH) and proopiomelanocortin (POMC)] peptides in male Wistar rats fed a standard laboratory diet. Furthermore, we evaluated the effects of EM-2 on dopamine (DA), norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) steady state concentrations, in the hypothalamus. 64 rats (16 for each group of treatment) were injected into the ARC, at 9.00 am, with either vehicle or EM-2 (0.50-0.75 μmol/kg) or EM-2 (0.50 μmol/kg) plus β-funaltrexamine (0.20 μmol/kg). Food intake was recorded through 24h following injection, and hypothalamic DA, NE, 5-HT levels and neuropeptide gene expression were evaluated 24h after EM-2 administration. Compared to vehicle, EM-2 significantly increased food intake, throughout 24h post-injection. Furthermore, EM-2 treatment led to a significant increase of DA and NE concentrations and a decrease of CRH mRNA levels. On the other hand, β-funaltrexamine administration reverted both feeding stimulatory and neuromodulatory effects induced by EM-2. We can conclude that the orexigenic effect of μ-opioid receptor activation by EM-2 could be related to both inhibition of CRH and stimulation of dopamine and norepinephrine levels, in the hypothalamus.

Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Corticotropin-Releasing Hormone; Dopamine; Feeding Behavior; Gene Expression Regulation; Humans; Hypothalamus; Intracellular Signaling Peptides and Proteins; Naltrexone; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Norepinephrine; Oligopeptides; Orexins; Pro-Opiomelanocortin; Rats; Serotonin

The present study investigated the effect of neuropeptide Y on nociception in the nucleus accumbens of rats. Intra-nucleus accumbens administration of neuropeptide Y induced dose-dependent increases in the hindpaw withdrawal latency (HWL) to thermal and mechanical stimulation in rats. There were no significant changes in the HWL to both stimulation during 60 min after the administration of NPY to outside of the nucleus accumbens. The anti-nociceptive effect of NPY was blocked by subsequent intra-nucleus accumbens injection of the Y1 receptor antagonist neuropeptide Y 28-36, indicating that Y1 receptor is involved in the neuropeptide Y-induced anti-nociception in the nucleus accumbens. Furthermore, the anti-nociceptive effect of neuropeptide Y was attenuated by intra-nucleus accumbens administration of the opioid antagonist naloxone, suggesting an involvement of the endogenous opioid system in the neuropeptide Y-induced anti-nociception in the nucleus accumbens of rats. Moreover, the neuropeptide Y-induced anti-nociception was attenuated by following intra-nucleus accumbens injection of the selective opioid antagonists nor-binaltorphimine and beta-funaltrexamine, but not by naltrindole, illustrating that mu- and kappa-opioid receptors, not the delta-opioid receptor, were involved in the neuropeptide Y-induced anti-nociception in the nucleus accumbens of rats.

Topics: Animals; Catheterization; Dose-Response Relationship, Drug; Hot Temperature; Male; Microinjections; Naloxone; Naltrexone; Narcotic Antagonists; Neuropeptide Y; Nucleus Accumbens; Pain Measurement; Peptide Fragments; Physical Stimulation; Rats; Rats, Wistar; Receptors, Neuropeptide Y; Receptors, Opioid

The non-selective opioid receptor antagonist naloxone decreases the robust feeding observed after i.c.v. injection of neuropeptide Y (NPY). In the present study we evaluated the effects of three selective opioid receptor antagonists on NPY-induced feeding. Graded doses of norbinaltorphimine (norBNI), beta-funaltrexamine (beta-FNA) and naltrindole (NTI), antagonists of the kappa, mu and delta receptors respectively, were preinjected (i.c.v.) in male rats prior to injection of 5 micrograms NPY (i.c.v.). Food intake was measured 1, 2 and 4 h post-NPY injection. Injection of beta-FNA and norBNI were most effective in reducing NPY-induced feeding, whereas NTI had little effect on NPY-induced feeding.

Topics: Animals; Eating; Injections, Intraventricular; Male; Naltrexone; Narcotic Antagonists; Neuropeptide Y; Rats; Rats, Sprague-Dawley