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M 1 and M 4 muscarinic receptors from hippocampus are positively involved in memory consolidation
Author(s) -
Jerusalinsky D.,
Kornisiuk E.,
Romanelli Ferreira A.,
Sánchez G.,
Fürstenau L.,
Blanco C.,
Cerveñansky C.,
Quillfeldt J.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.10_4.x
Subject(s) - muscarinic acetylcholine receptor , pirenzepine , receptor , memory consolidation , muscarinic acetylcholine receptor m1 , hippocampus , neuroscience , muscarinic acetylcholine receptor m4 , muscarinic acetylcholine receptor m2 , chemistry , muscarinic antagonist , hippocampal formation , amnesia , inhibitory postsynaptic potential , biology , pharmacology , endocrinology , psychology , biochemistry , psychiatry
The muscarinic antagonist scopolamine causes amnesia in rats, both systemically or administered into the hippocampus after training, supporting the involvement of muscarinic receptors (MAChR) in memory. The role of MAChR subtypes was poorly understood in vivo due to the lack of enough selective pharmacological tools. Central M 1 , M 3 and M 5 receptors are mainly coupled to the phosphoinositide pathway, while central M 2 and M 4 receptors couple to the inhibition of stimulated adenylate cyclase (AC). Muscarinic toxins (MTs) from Dendroaspis snakes venom are selective for MAChR subtypes. MT 1 and MT 2 , with affinity order M 1 M 4 other subtypes, behaved as M 1 agonists in various preparations. MT 3 is highly selective for M 4 receptors. These MTs fully antagonised the muscarinic inhibition of FSK‐stimulated hippocampal AC. As these MTs have negligible binding to M 2 receptor, the M 4 subtype must be responsible for most of the AC inhibition. Pirenzepine, an antagonist with similar affinity for M 1 and M 4 , given into the hippocampus after an inhibitory avoidance task was amnesic. MT 1 and MT 2 facilitated memory consolidation, corroborating the positive involvement of M 1 receptors. At a higher dose of MT 2 , the facilitation disappeared, suggesting that it was acting at another site, likely blocking M 4 receptors. These results strongly support that M 4 receptor of the hippocampus, responsible for muscarinic inhibition of AC, positively modulates memory consolidation.