U-50488H, a selective kappa-opioid receptor agonist, improves carbon monoxide-induced delayed amnesia in mice

European Journal of Pharmacology
M HiramatsuT Kameyama

Abstract

The effects of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulfonate salt (U-50488H) on carbon monoxide (CO)-induced amnesia in mice were investigated using spontaneous alternation and step-down type passive avoidance tasks. The lower percentage alternation and shorter median step-down latency in the retention test of the CO-exposed group indicated that memory deficiency occurred in mice when behavioral testing commenced 5-7 days after CO exposure. Administration of U-50488H (0.21 and 0.64 mumol/kg s.c.) 25 min before spontaneous alternation performance or the first training session of the passive avoidance task improved the CO-induced impairment of alternation performance and passive avoidance tasks. To determine whether the effect of U-50488H was mediated via kappa-opioid receptors, we attempted to block its action using a selective kappa-opioid receptor antagonist (nor-binaltorphimine). Nor-binaltorphimine (5.44 nmol/mouse i.c.v.) blocked the effect of U-50488H on CO-induced delayed amnesia. Furthermore, a low dose of scopolamine (0.41 mumol/kg s.c.) also blocked the ameliorating effect of U-50488H. U-50488H (0.21-2.15 mumol/kg s.c.) did not facilitate the acquisition of memory...Continue Reading

References

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Citations

Jul 10, 2013·Psychopharmacology·Ashlee Van't Veer, William A Carlezon
Apr 14, 2000·Behavioural Brain Research·P M Wall, C Messier
Apr 15, 2003·Progress in Neuro-psychopharmacology & Biological Psychiatry·Philip M WallD Caroline Blanchard
Jul 2, 2005·Expert Opinion on Investigational Drugs·A Barber, R Gottschlich

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