title: Centrally administered opioid antagonists, nor-binaltorphimine, 16-methyl cyprenorphine and MR2266, suppress intake of a sweet solution.
abstract: Three opioid antagonists (MR2266, 16-methyl cyprenorphine and nor-binaltorphimine) were tested independently for their ability to suppress the intake of a highly palatable saccharin and glucose (S/G) solution after central administration. MR2266 is an equally potent antagonist at kappa (kappa) and mu (mu) opioid receptors. Nor-binaltorphimine (N-BNI) and 16-methyl cyprenorphine (M80) are two recently developed opioid antagonists that were chosen based upon their ability to act more selectively than naloxone at kappa and delta (delta) opioid receptor types, respectively. Prior research has demonstrated that when dissolved in acid and administered centrally, MR2266 (20 micrograms) fails to suppress S/G intake. Because all three antagonists are rather insoluble in water, they were dissolved in dimethyl sulfoxide (DMSO). Rats with chronic ventricular cannula were allowed to consume S/G for a 0.5 hr bout. They received a single intracerebroventricular (ICV) injection of antagonist (MR2266: 0, 10, 20 and 40 micrograms; M80: 0, 5, 10, 20 and 40 micrograms or N-BNI: 0, 1, 3, and 10 micrograms) 10 min prior to the start of the drinking bout. Administration of DMSO alone failed to alter drinking relative to saline, whereas each antagonist significantly attenuated S/G intake. We conclude that, when dissolved in DMSO, these antagonists suppress drinking by blockade of opioid receptors.
authors.affiliation: Pharmacology Department, Emory University School of Medicine, Atlanta, GA 30322.
authors.forename: D J
authors.initials: DJ
authors.lastname: Calcagnetti
authors.forename: R L
authors.initials: RL
authors.lastname: Calcagnetti
authors.forename: M S
authors.initials: MS
authors.lastname: Fanselow
mesh_terms: D000818:Animals; D001575:Benzomorphans / Q000008:administration & dosage / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects*; D005260:Female; D005947:Glucose; D007276:Injections, Intraventricular; D009019:Morphinans / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin
chemical_list: D001575:Benzomorphans; D009019:Morphinans; D009292:Narcotic Antagonists; C051844:norbinaltorphimine; C051207:16-methylcyprenorphine; C027247:MR 2266; D009271:Naltrexone; D012439:Saccharin; D005947:Glucose