Blockade of spatial learning by the M1 muscarinic antagonist pirenzepine

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Abstract
Two experiments were conducted to determine the effects of the M1 muscarinic receptor antagonist pirenzepine on place navigation in a water maze. In the first experiment rats were required to learn the location of a hidden platform following intracerebroventricular injections of equimolar doses of pirenzepine or scopolamine methylbromide. Both drugs dose-dependently impaired spatial learning according to both escape latency data and transfer test analysis. Pirenzepine was approximately 3 times less potent than scopolamine, a potency ratio which suggests M1 receptor mediation of the impairment. In the second experiment pirenzepine (1∼92.3 μg/rat ICV) was injected prior to training on a simultaneous place dicrimination task in the water maze. Impairments of choice accuracy were found with a dose of 20 μg/rat in the absence of any marked increases in either errors of omission or choice latency. These data suggest that M1 receptor blockade impairs processes which are involved in spatial learning.