Modulation of ethanol state-dependent learning by dorsal hippocampal NMDA receptors in miceAlcohol Article in Press 9 September 2008
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 μg/mouse) by itself had no effect on memory retrieval and ethanol-induced 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 μg/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 μg/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 μg/mouse) alone did not affect memory retention.
It may be concluded that dorsal hippocampal NMDA receptors are involved in mediating ethanol state-dependent learning.
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