Spermidine, a polyamine site agonist, attenuates working memory deficits caused by blockade of hippocampal muscarinic receptors and mGluRs in rats.

Spermidine, an agonist of the polyamine site on the NMDA receptor/channel complex, did not affect the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points) in the working memory task with a three-panel runway setup, when injected bilaterally at 1 or 10 microg/side into the dorsal hippocampus. Intrahippocampal administration of the muscarinic receptor antagonist scopolamine (3. 2 microg/side) significantly increased the number of working memory errors. The increase in working memory errors by intrahippocampal 3. 2 microg/side scopolamine was significantly reduced by concurrent infusion of 10 microg/side spermidine. Likewise, spermidine (10 microg/side) was effective in attenuating the increase in working memory errors induced by intrahippocampal administration of AIDA (3. 2 microg/side), a potent and selective antagonist of the class I metabotropic glutamate receptor (mGluR). These results suggest that enhanced NMDA function via polyamine modulatory site on the NMDA receptor/channel can compensate dysfunction of hippocampal cholinergic and mGluR-mediated neurotransmission involved in working memory function.