Abstract
Intrahippocampal administration of the histamine H 1 receptor antagonist pyrilamine (3.2–32 μg/side) but not the histamine H 2 receprtor antagonist cimetidine (1.0–10 μg/side) increased the number of errors in the working memory task with a three-panel runway setup. The increase in working memory errors induced by intrahippocampal 32 μg/side pyrilamine was significantly reduced by concurrent infusion of the histamine H 1 receptor agonist 2-pyridylethylamine (3.2 and 10 μg/side). The cholinesterase inhibitor physostigmine (1.0 and 3.2 μg/side) and d-cycloserine (0.32 and 1.0 μg/side), the partial agonist at the glycine binding site on the NMDA receptor/channel complex, reduced the increase in working memory errors induced by intrahippocampal 32 μg/side pyrilamine. These results suggest that the hippocampal histaminergic activity via histamine H 1 receptor is necessary for normal working memory processes and that the septohippocampal cholinergic activation and positive modulation of the NMDA receptor/channel through activation of the glycine site can alleviate dysfunction of hippocampal histamine H 1 receptor-mediated neurotransmission involved in working memory function.
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