Memory of inhibitory avoidance in the rat is regulated by glutamate metabotropic receptors and by calcium/calmodulin kinase II in the hippocampus

ABSTRACT

We studied the effect on memory of the bilateral intrahippocampal posttraining infusion of the glutamate metabotropic receptor (mGLUR) agonist, 1S,2R-aminocyclopentane dicarboxylate (ACPD), of the mGLUR antagonist, [RS]-alpha-methyl-4-carboxyphenyl glycine (MCPG), and of the inhibitor of calcium/calmodulin protein kinase II (CaM II), 1-[N,O-Bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl piperazine (KN62). Male Wistar rats were implanted with cannulae in the CA1 region of the dorsal hippocampus. After recovery from surgery they were trained in a step-down inhibitory avoidance task and tested for retention 24 h later. Immediately or 180 min after training they received an intrahippocampal infusion of saline (0.5 mul), KN62 (100 mumoles), ACPD (20 nmoles), MCPG (13 nmoles) or of ACPD plus MCPG in 0.5 mul of saline. When given immediately after training, KN62 and MCPG were amnestic and ACPD caused memory facilitation and antagonized the effect od MCPG. When given 180 min after training, the drugs had no effect on memory. The results indicate that the early phase of memory is regulated by mGLURs in the hippocampus and requires CaM II activity. The data support the suggestion that memory involves long-term potentiation in the hippocampus.