naloxone and xenin-25

We recently reported that the 25 amino acid peptide xenin caused reduced feed intake when centrally injected in chicks. The present study was designed to explore possible mechanisms of the xenin-induced anorexigenic response in chicks. In Experiments 1 and 2, chicks were implanted with cannulas and xenin injections were made directly into the ventromedialis hypothalami (VMH). Chicks responded with reduced feed intake and increased c-Fos immunoreactivity at the VMH. In Experiment 3 chicks that received co-intracerebroventricular (ICV) injection of naloxone and a dose of xenin (100 pmol), that alone does not affect feed intake, had reduced feed intake. In Experiment 4, chicks responded to ICV xenin with reduced feed- but increased exploratory-pecking. Thus, we conclude that xenin may mediate its effect directly at the VMH and that the endogenous opioid system may counter anorexigenic effects of low xenin doses in chicks. Xenin also caused increased exploration of a novel environment, an effect that may be competitive with feeding. Taken together, these results suggest that xenin regulation of chick appetite is the result of several central and behavioral mechanisms acting in synergism.

Topics: Analgesics, Opioid; Animals; Anorexia; Appetite Regulation; Chickens; Eating; Feeding Behavior; Naloxone; Narcotic Antagonists; Neurotensin; Peptides; Proto-Oncogene Proteins c-fos; Receptors, Opioid

Central feeding regulation involves both anorectic and orexigenic pathways. This study examined whether targeting both systems could enhance feeding inhibition induced by anorectic neuropeptides.. Experiments were carried out in 24-hour fasted rats. Intracerebroventricular (ICV) injections were accomplished through stereotaxically implanted cannulae aimed at the lateral cerebral ventricle. Food intake of standard rat chow pellets was subsequently recorded for 2 hours.. Blockade of orexigenic central opioids and neuropeptide Y (NPY) by ICV naloxone (25 microg) or the NPY receptor antagonist [D-Trp32]NPY (NPY-Ant; 10 micro g) powerfully augmented the feeding suppression induced by ICV glucagon-like peptide 1 (7-36)-amide (GLP-1; 10 microg) or xenin-25 (xenin; 15 microg) in 24-hour fasted rats. Most importantly, in combination with naloxone or NPY-Ant, even a low and ineffective dose of GLP-1 (5 microg) caused a 40% reduction of food intake, which was augmented further when both antagonists were given in combination with GLP-1. The combination of GLP-1 (5 microg) and xenin (10 microg) at individually ineffective doses caused a 46% reduction of food intake, which was abolished at a 10-fold lower dose. This ineffective dose, however, reduced food intake by 72% when administered in combination with naloxone and NPY-Ant.. Targeting up to four pathways of feeding regulation in the central nervous system by blockade of endogenous feeding stimuli and simultaneous administration of anorectic neuropeptides potentiated reduction of food intake. This raises a promising perspective for treatment of obesity.

Topics: Animals; Appetite Depressants; Eating; Glucagon; Glucagon-Like Peptide 1; Homeostasis; Male; Naloxone; Narcotic Antagonists; Neuropeptide Y; Neuropeptides; Neurotensin; Peptide Fragments; Peptides; Protein Precursors; Rats; Rats, Wistar; Receptors, Neuropeptide Y