title: Influence of N-methyl D-aspartate receptor mechanism on WIN55,212-2-induced amnesia in rat dorsal hippocampus.
abstract: In this study, we investigated the effects of both N-methyl D-aspartate (NMDA) and MK-801 on WIN55,212-2(WIN)-induced amnesia in rats. Step-through inhibitory avoidance of memory was used to examine the retrieval of memory, 24 h after training. All drugs were injected bilaterally into the dorsal hippocampus (intra-CA1) of rats. Pretraining and posttraining or pretesting administration of the nonselective CB1/CB2 receptor agonist, WIN (0.5 µg/rat), decreased the step-through latency. However, amnesia induced by pretraining or posttraining injections of WIN was reversed by a pretest administration of WIN (0.25 and 0.5 µg/rat). Pretest microinjections of different doses of NMDA (0.1, 0.5, and 1 µg/rat) elicited no response, but NMDA (0.5 and 1 µg/rat) did induce full recovery from amnesia induced by WIN (0.5 µg/rat). The posttraining and pretest injection of a higher dose of the NMDA receptor antagonist, MK801 (MK; 4 µg/rat), caused an impairment in the memory retrieval. However, amnesia induced by posttraining injections of MK (4 µg/rat) was reversed by a pretest administration of MK (4 µg/rat). In addition, pretest administration of different doses of the antagonist (2 and 4 µg/rat) induced full recovery of WIN-induced amnesia, but did not influence memory recovery in the subjects, which had received posttraining (0.5 µg/rat) and pretest WIN (0.25 and 0.5 µg/rat). Pretesting coadministration of ineffective doses of WIN (0.1 µg/rat) with NMDA (0.1 µg/rat), but not with MK (1 µg/rat), restored WIN-induced (0.5 µg/rat) amnesia. It can be concluded that the NMDA receptor mechanism located in the dorsal hippocampus may be involved in WIN-induced amnesia.
authors.affiliation: Institute for Cognitive Science Studies, Department of Physiology, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nida
authors.initials: N
authors.lastname: Jamali-Raeufy
authors.forename: Mohammad
authors.initials: M
authors.lastname: Nasehi
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Zarrindast
mesh_terms: D000647:Amnesia / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D006624:Hippocampus / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning; D008568:Memory / Q000502:physiology; D008570:Memory, Short-Term; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D016291:Dizocilpine Maleate