norbinaltorphimine and Carbon-Monoxide-Poisoning

The effects of dynorphin A (1-13) on carbon monoxide (CO)-induced amnesia in mice were investigated. Memory deficiency was apparent during Y-maze testing 5 days after CO exposure (delayed amnesia). Percent alternation in the CO-exposed group was significantly lower than that in the control group. Administration of dynorphin A (1-13) (1.5 nmol, i.c.v.) 15 min before the Y-maze test session reversed the impairment of spontaneous alternation performance in the CO-exposed group. To determine whether this effect was mediated via kappa opioid receptors, we attempted to block the effect of dynorphin A using the kappa opioid receptor antagonist nor-binaltorphimine. Nor-binaltorphimine (5.44 nmol, i.c.v.) blocked the effect of dynorphin A (1-13) on delayed amnesia. Dynorphin A (1-13) did not affect the impairment of alternation induced by the blockade of NMDA-receptors by dizocilpine (MK-801), but significantly prevented the impairment induced by mecamylamine. These results suggest that dynorphin A (1-13) modulates the kappa receptor-mediated opioid neuronal system, and reverses the impairment of spontaneous alternation performance induced by CO exposure.

Topics: Amnesia; Animals; Carbon Monoxide Poisoning; Dizocilpine Maleate; Dynorphins; Excitatory Amino Acid Antagonists; Injections, Intraventricular; Male; Maze Learning; Mecamylamine; Mice; Mice, Inbred Strains; Naltrexone; Narcotic Antagonists; Narcotics; Nicotinic Antagonists; Peptide Fragments; Receptors, N-Methyl-D-Aspartate; Receptors, Opioid, kappa

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 in normal mice. These results suggest that U-50488H modulates the kappa-opioid receptor-mediated opioid neuronal system and activates the cholinergic neuronal system, and that it ameliorates the disruptive effect of CO on acquisition and/or consolidation of memory.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Amnesia; Analgesics; Animals; Avoidance Learning; Carbon Monoxide Poisoning; Electric Stimulation; Male; Mice; Naltrexone; Narcotic Antagonists; Pyrrolidines