• Ameneh Rezayof, Zahra Shirazi-Zand, Mohammad-Reza Zarrindast, and Touraj Nayer-Nouri.
• Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. rezayof@khayam.ut.ac.ir
• Life Sci. 2010 Feb 13;86(7-8):260-6.

AimsThe current study was undertaken to determine the role of dorsal hippocampal N-methyl-d-aspartate (NMDA) receptors in nicotine's effect on impairment of memory by ethanol.Main MethodsAdult male mice were cannulated in the CA1 regions of dorsal hippocampi and trained on a passive avoidance learning task for memory assessment.Key FindingsWe found that pre-training intraperitoneal (i.p.) administration of ethanol (0.5 and 1g/kg) decreased memory retrieval when tested 24h later. Pre-test administration of ethanol reversed the decrease in inhibitory avoidance response induced by pre-training ethanol. Similar to ethanol, pre-test administration of nicotine (0.125-0.75 mg/kg, s.c.) prevented impairment of memory by pre-training ethanol. In the animals that received ethanol (1g/kg, i.p) before training and tested following intra-CA1 administration of different doses of NMDA (0.0005-0.005 microg/mouse), no significant change was observed in the retrieval latencies. Co-administration of the same doses of NMDA with an ineffective dose of nicotine (0.125 mg/kg, s.c.) significantly improved the memory retrieval and mimicked the effects of pre-test administration of a higher dose of nicotine. Pre-test intra-CA1 microinjection of MK-801 (0.25-1 microg/mouse), which had no effect alone, in combination with an effective dose of nicotine (0.75 mg/kg, s.c.) prevented the improving effect of nicotine on memory impaired by pre-training ethanol. Moreover, intra-CA1 microinjection of MK-801 reversed the NMDA-induced potentiation of the nicotine response.SignificanceThe results suggest the importance of NMDA glutamate system(s) in the CA1 regions of dorsal hippocampus for improving the effect of nicotine on the ethanol-induced amnesia.Copyright 2009 Elsevier Inc. All rights reserved.

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