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

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 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 M1 receptor subtype coupling systems seem to be more important in the acquisition-consolidation process rather than in the retrieval process.