The ameliorating effects of NMDA receptor agonists on histamine H1 antagonist-induced memory and hippocampal theta disruptions are prevented by the H3 receptor agonist in rats

In the present study, we investigated the effect of imetit, a selective histamine H3 agonist, on the improvement of NMDA receptor agonists in H1 antagonist-induced working memory deficit and the decrease of hippocampal theta activity in rats. Pyrilamine (35 mg/kg, i.p.) impaired spatial memory and decreased hippocampal theta activity during the radial maze task. In addition, intrahippocampal injection of d-cycloserine (1 μg/side) and spermidine (10 μg/side) improved the pyrilamine-induced working memory deficit and the decrease of hippocampal theta activity. The improvement effects of d-cycloserine and spermidine were antagonized by intrahippocampal injection of imetit (10 μg/side). These results indicate that, the facilitation of neurotransmitter release from the presynaptic terminals besides direct stimulation of postsynaptic NMDA receptors take part in the improvements of NMDA receptor agonists on pyrilamine-induced spatial memory deficit and the decrease of hippocampal theta activity.