Effects of combined methysergide and mecamylamine/scopolamine treatment on spatial navigation.

In the present study, we investigated the effects of a 5-HT2 receptor antagonist, methysergide (2.5, 7.5 and 20 mg/kg), on spatial learning in saline, mecamylamine (10 mg/kg) and scopolamine (0.8 mg/kg) treated rats. Methysergide had no effect on water-maze (WM) spatial learning in rats subjected to saline or mecamylamine pretreatments. However, scopolamine-induced WM learning deficit was augmented by methysergide at doses of 7.5 and 20 mg/kg. These results further suggest (A) that cholinergic and serotonergic systems may interact in the regulation of spatial learning, and (B) that the cholinergic component of this interaction with serotonin2 receptors is mediated by muscarinic receptors, but not by nicotinic receptors.