Learning and MemoryWorking memory failure by combined blockade of muscarinic and β-adrenergic transmission in the rat hippocampusOhno, Masuo1,2; Kobayashi, Masako1; Kishi, Akihiro1; Watanabe, Shigenori1Author Information 1Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-82, Japan 2Corresponding Author: Masuo Ohno Received 28 January 1997; accepted 5 March 1997 NeuroReport: May 6, 1997 - Volume 8 - Issue 7 - p 1571-1575 Buy Abstract INTRAHIPPOCAMPAL administration of the muscarinic acetylcholine receptor antagonist scopolamine at a dose of 3.2 μg/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 μg/side scopolamine did not affect working memory errors. The β-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 μg/side). The increase in working memory errors induced by intrahippocampal administration of 0.32 μg/side scopolamine to rats treated with 10 mg/kg propranolol was decreased by concurrent injection of the cholinesterase inhibitor physostigmine (3.2 μg/side). D-Cycloserine (the partial agonist at the glycine binding site on the NMDA receptor/channel complex) at a dose of 10 μg/side reduced the increase in working memory errors induced by intrahippocampal 0.32 μg/side scopolamine combined with 10 mg/kg propranolol. These results suggest that neural mechanisms regulated cooperatively by hippocampal muscarinic and β-adrenergic transmission underlie working memory performance, and that modification of NMDA function contributes to such interactive regulation of working memory processes in the hippocampus. © Lippincott-Raven Publishers.