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.
Kishi
A
A
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-82, Japan.
Ohno
M
M
Watanabe
S
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects*; D008845:Microinjections; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000502:physiology; D012601:Scopolamine / Q000008:administration & dosage; D013095:Spermidine / Q000008:administration & dosage* / Q000378:metabolism
D011073:Polyamines; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104077:metabotropic glutamate receptor type 1; D012601:Scopolamine; D013095:Spermidine