Evidence for a preferential involvement of M1 muscarinic receptors in representational memory

The effects of intrahippocampal injections to the M1-selective antagonist pirenzepine and the M2-selective antagonist AF-DX 116 were examined on performance of a representational memory task in rats. Although both antagonists impaired performance, pirenzepine was more potent than AF-DX 116. Pirenzepine (70.8 +/- 2.8% correct) produced a greater deficit than AF-DX 116 (83.3 +/- 0.0%) at 70 micrograms, and the deficit at 10 micrograms (83.3 +/- 2.8%) was equal to that produced by 70 micrograms of AF-DX 116. The data provide additional support for the cholinergic hypothesis of memory and new information regarding the subtypes of muscarinic receptors likely to be involved in representational memory. Based on the greater susceptibility of representational memory to the effects of pirenzepine, it is suggested that M1 receptors in the hippocampus play a greater role in memory function than M2 receptors.