Effects of Selective Muscarinic Antagonists, Pirenzepine and AF-DX 116,on Passive Avoidance Tasks in Mice

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To clarify the physiological roles of muscarinic acetylcholine (mACh) receptor subtypes, M_1 and M_2,on learning and memory, we examined the effects of three antagonists, atropine (non-selective), pirenzepine (M_1 selective) and 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one, AF-DX 116 (M_2 selective), on step-through passive avoidance tasks in mice. During acquisition tests, mice were trained repeatedly until they achieved criterion latency (300 s). In all experiments, drugs or vehicles were intracerebroventricularly administered. Pre-training (5 min before) administration of atropine (1-40 nmol) and pirenzepine(10 and 40 nmol) shortened the response latency in retention tests at 14 d after acquisition training. Pre-test (5 min before) and post-training (immediately after the acquisition training) administration of atropine slightly but not significantly impaired retention scores. The administration of AF-DX 116 did not apparently affect the scores in any of tests. Thus, the M_1 receptor subtype coupling systems seem to be more important in the acquisition-consolidation process rather than in the retrieval process.
公益社団法人日本薬学会の論文
1996-06-15