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Paper   IPM / Cognitive Sciences / 9608
School of Cognitive Sciences
  Title:   Modulation of ethanol state-dependent learning by dorsal hippocampal NMDA receptors in mice
  Author(s): 
1.  A. Rezayof
2.  K. Sharifi
3.  M.R. Zarrindast
4.  Y. Rassouli
  Status:   Published
  Journal: Alcohol
  No.:  42
  Year:  2008
  Pages:   667-674
  Supported by:  IPM
  Abstract:
The possible role of N-methyl-D-aspartate (NMDA) receptors of dorsal hippocampus on ethanol state-dependent learning was studied in adult male mice (Pasteur Institute, Iran). As a model of memory, a single-trial step-down passive avoidance task was used. All animals were bilaterally implanted with cannulae into the CA1 regions of dorsal hippocampi. Results show that intraperitoneal (i.p.) administration of ethanol (0.5 and 1 g/kg) 30 min before training impaired memory performance in animals when tested 24 h later. Pretest administration of the same doses of ethanol-induced state-dependent retrieval of the memory acquired under pretraining ethanol (1 g/kg, i.p.) influence. Pretest intra-CA1 microinjection of NMDA (0.001, 0.01, and 0.1 mg/mouse) by itself had no effect on memory retrieval and ethanolinduced amnesia. However, pretest intra-CA1 administration of the same doses of NMDA with an ineffective dose of ethanol (0.25 g/kg, i.p.) significantly restored the retrieval and potentiated ethanol state-dependent learning. On the other hand, pretest administration of a competitive NMDA receptor antagonist D-AP5 (D-( -2-Amino-5-phosphonopentanoic acid) (0.01, 0.1, and 1 mg/mouse, intra-CA1) or a noncompetitive NMDA receptor antagonist MK-801 maleate [(5S, 10R)-(�)-5-Methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine maleate] (0.25, 0.5, and 1 g/mouse, intra-CA1) 5 min before the administration of ethanol (1 g/kg, i.p.) significantly inhibited ethanol state-dependent learning. Intra-CA1 pretest administration of D-AP5 (0.01, 0.1, and 1 mg/mouse) or MK-801 maleate [5S, 10R)- (�)-5-Methyl-10, 11-dihydro-5H-dibenzo [a, d] cyclohepten-5, 10-imine maleate] (0.25, 0.5, and 1 mg/mouse) alone did not affect memory retention. It may be concluded that dorsalhippocampal NMDA receptors are involved in mediating ethanol state-dependent learning.

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