Participation of hippocampal ionotropic glutamate receptors in histamine H1 antagonist-induced memory deficit in rats

Abstract

Pyrilamine, a selective histamine H(1) antagonist, impaired spatial memory, and decreased hippocampal theta activity during a radial maze task. We investigated the ameliorative effects of glutamatergic drugs on pyrilamine-induced spatial memory deficit and the decrease in hippocampal theta activity in rats. Drug effects were measured using an eight-arm radial maze with four arms baited. Hippocampal theta rhythm during the radial maze task was also recorded with a polygraph system using a telemetric technique. Intraperitoneal injection of pyrilamine (35 mg/kg) resulted in impaired reference and working memory in the radial maze task and a decrease in the amplitude and power of hippocampal theta waves. The working memory deficit and the decrease in hippocampal theta power were antagonized by intrahippocampal injection of D: -cycloserine (1 microg/side), spermidine (10 microg/side), spermine (10 microg/side), aniracetam (1 microg/side), and 1-(1,3-benzodioxol-5-ylcarbonyl) piperidine (1-BCP) (1 microg/side), but not concanavalin A. These results clearly indicate that H(1) antagonist-induced working memory deficit, and the decrease in hippocampal theta activity was closely associated with hippocampal glutamatergic neurotransmission mediated by N-methyl-D: -aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.