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 μmol/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 μmol/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 μmol/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 μmol/kg each) did not have any additive or antagonizing effects on the percent alternation. An antinociceptive effect was observed only with (−)-pentazocine (3.50 μmol/kg, s.c.), and was antagonized by nor-binaltorphimine (4.9 nmol/mouse, i.c.v.), but not by NE-100 (2.6 μmol/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.