Establishment and estimation of pharmacological bioassay system for therapeutic drugs of aging in central nervous system.

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To clarify the physiological roles of muscarinic acetylcholine (mACh) receptor subtypes, M1 and M2, on learning and memory, we examined the effects of three antagonists, atropine (non-selective), pirenzepine (M1 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 (M2 selective), on stpe-through passive avoidance tasks in mice. Pre-training (5min 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 (5min befor) and post-training (immediately after the acquisition) 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 M1 receptor subtype coupling systemes seem to be more important in the acquisition-consolidation process rather than in the retrieval process.