The kappa-opioid antagonist GNTI reduces U50,488-, DAMGO-, and deprivation-induced feeding, but not butorphanol- and neuropeptide Y-induced feeding in rats

Antagonists selective for either kappa- [e.g. nor-binaltorphimine (nor-BNI) ] and mu- (e.g. beta-funaltrexamine) opioid receptors have previously been shown to reduce both kappa- and mu-opioid-induced feeding. In the present s tudies, the anorectic effects of GNTI, a newly synthesized antagonist selec tive for kappa-opioid receptors, were studied in rats. GNTI (0.032-0.32 nmo l; i.c.v.), administered 15 min prior to food access, reduced feeding induc ed by the kappa-opioid agonist U50,488 (producing a 70% maximal decrease), the mu-opioid agonist DAMGO (90% maximal decrease), and 24 h acute food dep rivation (60% maximal decrease). GNTI did not reduce the orexigenic effects of butorphanol, an agonist that binds to both kappa- and mu-opioid recepto rs, and neuropeptide Y (NPY). Taken together, these results suggest that GN TI is a potent anorectic agent and opioid antagonist in rats. Like nor-BNI, GNTI reduced feeding induced by both kappa- and mu-opioid agonists. Howeve r, unlike nor-BNI, GNTI did not alter the orexigenic effects of butorphanol or NPY. Given the selectivity of GNTI and its effectiveness in several of the present experiments, its potency, and its short duration of action comp ared to nor-BNI, GNTI may serve to be a useful tool to study behavioral eff ects mediated by kappa-opioid receptors. (C) 2001 Published by Elsevier Sci ence B.V.