Ameliorative Effect of a Hippocampal Metabotropic Glutamate–Receptor Agonist on Histamine H1 Receptor Antagonist–Induced Memory Deficit in Rats

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This study was performed to investigate the ameliorative effects of metabotropic glutamate (mGlu)-receptor agonists on histamine H1 receptor antagonist–induced spatial memory deficit and the decrease in hippocampal theta activity in rats. Intraperitoneal injection of pyrilamine (35 mg/kg) resulted in impaired reference and working memory in the radial maze task and decreased hippocampal theta amplitude and power. The working memory deficit and decreased hippocampal theta power induced by pyrilamine were ameliorated by intrahippocampal injection of (RS)-3,5-dihydroxyphenylglycine (DHPG) (1 and 10 μg/side), a group I mGlu-receptor agonist; however, intrahippocampal injection of (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (APDC), a group II mGlu-receptor agonist, and L-(+)-2-amino-4-phosphonobutyric acid (L-AP4), a group III mGlu-receptor agonist, showed no significant effect on the pyrilamine-induced memory deficit and decreased hippocampal theta activity. These results indicate that the activation of hippocampal group Ι mGlu receptors, but not group II and III mGlu receptors, improve the histamine H1 receptor antagonist–induced working memory deficit and decreased hippocampal theta activity.