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.
Saito
Shunsuke
S
Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Okada
Akiko
A
Ouwa
Takako
T
Kato
Akane
A
Akagi
Masaaki
M
Kamei
Chiaki
C
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D016291:Dizocilpine Maleate; D016572:Cyclosporine; D019703:Calcineurin