Cholinergic receptor agonists inhibit pirenzepine-induced dysfunction of spontaneous alternation performance in the mouse.

1. The present study was designed to examine the effects of intracerebroventricular injection of several cholinergic drugs on the impairment of spontaneous alternation performance induced by the M1-selective muscarinic receptor antagonist pirenzepine. 2. Pirenzepine (3 and 10 micrograms) significantly reduced spontaneous alteration performance related to working memory without producing any marked increase in total arm entries, which are considered to reflect locomotor activity. 3. Physostigmine (3.47 micrograms), a cholinesterase inhibitor, and McN-A-343 (20 micrograms), and M1-selective muscarinic receptor agonist, significantly improved the pirenzepine (3 micrograms)-induced impairment of spontaneous alternation performance, although oxotremorine (0.68 microgram), a nonselective muscarinic receptor agonist, showed a tendency to reverse the pirenzepine (3 micrograms)-induced impairment. 4. These findings suggest that the blockade of muscarinic M1 but not M2 receptors results in the impairment of spontaneous alternation performance associated with working memory.