Improvement of memory impairment by (+)- and (-)-pentazocine via sigma, but not kappa opioid receptors.
(+/-)-Pentazocine is widely used clinically to treat mild to moderate pain as a racemic compound. Although it is known that (-)-pentazocine acts as a kappa opioid receptor agonist to exhibit analgesic actions and (+)-pentazocine acts as a sigma receptor agonist without analgesic effects, their combined effect on memory has not been investigated in detail. In this study, the effect of (+)- and/or (-)-pentazocine on scopolamine-induced memory impairment in mice was investigated using spontaneous alternation performance in a Y-maze. (+)-Pentazocine (0.35 micromol/kg, s.c.) administered 30 min before behavioral testing significantly improved the impairment of spontaneous alternation induced by scopolamine. A higher dose of (-)-pentazocine (3.50 micromol/kg, s.c.) also reversed the scopolamine-induced impairment of alternation performance. Interestingly, the ameliorating effects of not only (+)-pentazocine, but also (-)-pentazocine were antagonized by a selective sigma receptor antagonist, N,N-dipropyl-2-[4-methoxy-3-(2-phenylenoxy)-phenyl]-ethylamine monohydrochloride (NE-100) (2.6 micromol/kg, i.p.). However, those effects were not antagonized by a selective kappa opioid receptor antagonist, nor-binaltorphimine (4.9 nmol/mouse, i.c.v.). Coadministration of (+)- and (-)-pentazocine (0.35 or 3.50 micromol/kg each) did not have any additive or antagonizing effects on the percent alternation. An antinociceptive effect was observed only with (-)-pentazocine (3.50 micromol/kg, s.c.), and was antagonized by nor-binaltorphimine (4.9 nmol/mouse, i.c.v.), but not by NE-100 (2.6 micromol/kg, i.p.). These results suggest that although the analgesic effect of pentazocine was mediated via kappa opioid receptors, the ameliorating effect on scopolamine-induced impairment of spontaneous alternation was mediated via sigma receptors, not via kappa opioid receptors.
Hiramatsu
Masayuki
M
Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human Sciences, Tenpaku-ku, Nagoya 468-8503, Japan. mhiramt@ccmfs.meijo-u.ac.jp
Hoshino
Takashi
T
D019342:Acetic Acid; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D000704:Analysis of Variance; D000818:Animals; D000840:Anisoles / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D007536:Isomerism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D009292:Narcotic Antagonists / Q000008:administration & dosage; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D010423:Pentazocine / Q000627:therapeutic use*; D011437:Propylamines / Q000494:pharmacology; D017473:Receptors, Opioid, kappa / Q000502:physiology; D017480:Receptors, sigma / Q000502:physiology*; D012601:Scopolamine
D000701:Analgesics, Opioid; D000840:Anisoles; D014150:Antipsychotic Agents; D009292:Narcotic Antagonists; D011437:Propylamines; D017473:Receptors, Opioid, kappa; D017480:Receptors, sigma; C083832:N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride; C051844:norbinaltorphimine; D009271:Naltrexone; D012601:Scopolamine; D019342:Acetic Acid; D010423:Pentazocine