Methoctramine moderately improves memory but pirenzepine disrupts performance in delayed non-matching to position test

The present study was designed to investigate the effect of i.c.v. administration of various muscarinic receptor antagonists in rats on memory performance in delayed non-matching to position test. The drugs chosen were the non-selective antagonist scopolamine (3 and 10 μg), the muscarinic M 1 receptor-selective antagonist pirenzepine (10 and 30 μg) and the muscarinic M 2 receptor-selective antagonist methoctramine (2, 5 and 20 μg). Scopolamine delay-independently decreased % correct choices and reduced motor activity. Pirenzepine also delay-independently decreased % correct choices. In contrast, methoctramine 2 μg, but not at 5 or 20 μg, improved slightly, but significantly, % correct performance delay-dependently. The present data suggests that the decrease in activation of inhibitory muscarinic M 2 autoreceptors induced by methoctramine produces a specific improvement of short-term memory at long forgetting delays.