Naloxone benzoylhydrazone, a kappa 3 opioid agonist, stimulates food intake in rats

• Published in: Brain research Vol. 581; no. 2; p. 311
• Main Authors: Koch, J E, Pasternak, G W, Arjune, D, Bodnar, R J
• Format: Journal Article
• Language: English
• Published: Netherlands 29-05-1992
• Subjects: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics - pharmacology; Animals; Cerebral Ventricles - drug effects; Cerebral Ventricles - physiology; Dose-Response Relationship, Drug; Feeding Behavior - drug effects; Infusions, Parenteral; Male; Naloxone - administration & dosage; Naloxone - analogs & derivatives; Naloxone - pharmacology; Pyrrolidines - pharmacology; Rats; Rats, Wistar; Receptors, Opioid, kappa - drug effects; Receptors, Opioid, kappa - physiology; Reference Values
• ISSN: 0006-8993
• DOI: 10.1016/0006-8993(92)90723-M

Naloxone benzoylhydrazone (NalBzoH) is a selective, short-acting agonist at the kappa 3 opioid receptor and a slowly dissociating potent antagonist at the mu opioid receptor. Given the important role of kappa receptors in the opioid control of food intake, the present study examined the central and peripheral effects of NalBzoH upon food intake. Central administration of NalBzoH (1-20 micrograms, i.c.v.) significantly increased food intake for up to 12 h, but failed to alter intake or body weight after 24 or 48 h. The 12 h duration of NalBzoH-mediated effects may be due to either persistent kappa 3 receptor occupancy, and/or activation of an ingestive system which maintains its activity. Peripheral administration of NalBzoH (20 mg/kg, s.c.) significantly increased food intake for up to 1 h. To distinguish kappa 1 (U50,488H) and kappa 3 (NalBzoH) hyperphagic effects, these agonist effects were compared following pretreatment with either naltrexone or the kappa 1 antagonist, nor-binaltorphamine (Nor-BNI). Whereas naltrexone significantly reduced both U50,488H and NalBzoH hyperphagia, Nor-BNI blocked U50,448H, but not NalBzoH hyperphagia. These data indicate a distinct role for the kappa 3 receptor in ingestive behavior separable from that of kappa 1 effects.