Working memory failure by combined blockade of muscarinic and beta-adrenergic transmission in the rat hippocampus.
INTRAHIPPOCAMPAL administration of the muscarinic acetylcholine receptor antagonist scopolamine at a dose of 3.2 micrograms/side significantly increased 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, whereas 0.32 microgram/side scopolamine did not affect working memory errors. The beta-adrenoceptor antagonist propranolol (10 mg/kg, i.p.) had no effect on working memory error, but it produced a significant increase in working memory errors when administered in combination with intrahippocampal scopolamine at the behaviourally ineffective dose (0.32 microgram/side). The increase in working memory errors induced by intrahippocampal administration of 0.32 microgram/side scopolamine to rats treated with 10 mg/kg propranolol was decreased by concurrent injection of the cholinesterase inhibitor physostigmine (3.2 micrograms/side). D-Cycloserine (the partial agonist at the glycine bindings site on the NMDA receptor/channel complex) at a dose of 10 micrograms/side reduced the increase in working memory errors induced by intrahippocampal 0.32 microgram/side scopolamine combined with 10 mg/kg propranolol. These results suggest that neural mechanisms regulated cooperatively by hippocampal muscarinic and beta-adrenergic transmission underlie working memory performance, and that modification of NMDA function contributes to such interactive regulation of working memory processes in the hippocampus.
Ohno
M
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kobayashi
M
M
Kishi
A
A
Watanabe
S
S
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D008568:Memory / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D018727:Muscarinic Antagonists; D011433:Propranolol; D012601:Scopolamine