Interaction between hippocampal gamma-aminobutyric acid(A) and N-methyl-D-aspartate receptors in the retention of spatial working memory in rats.

To clarify the interaction between hippocampal gamma-aminobutyric acid (GABA)(A) receptor and N-methyl-D-aspartate (NMDA) receptor in the retention of spatial working memory, the effects of muscimol, (+)MK-801, cyclosporin A and combined use of these drugs were studied on the retention of spatial working memory in a delayed spatial win-shift (SWSh) task. Intrahippocampal injection of muscimol at a dose of 3 nmol/side caused a significant decrease in the number of correct choices and an increase in the number of across-phase errors. On the other hand, (+)MK-801 showed no significant effect on the number of correct choices, across-phase errors and within-phase errors, even at a dose of 1.5 nmol/side; however, (+)MK-801 1.5 nmol/side significantly potentiated the effect of muscimol observed at a dose of 3 nmol/side on the number of correct choices and across-phase errors. Cyclosporin A at a dose of 3 nmol/side, which showed no effect when used separately, significantly potentiated the effect of muscimol observed at a dose of 3 nmol/side. These results indicate that hippocampal NMDA receptors regulate the effect of spatial working memory induced by muscimol. In addition, calcineurin may be involved in muscimol-induced impairment of memory retention.