The effects of increased serotonergic and decreased cholinergic activities on spatial navigation performance in rats.

In the present set of experiments the effects of a serotonin (5-HT) reuptake blocker, alaproclate (alap) and of a muscarinic antagonist, scopolamine (scop) on place navigation (hidden platform) and cued navigation (visible platform) water maze tasks were investigated. In hidden platform experiments it was observed that scopolamine (0.8 mg/kg) impaired performance (increased escape distance). Alaproclate 7.5 mg/kg and 20 mg/kg, but not 2.5 mg/kg produced a significant impairment. The combination of the highest dose of alaproclate (20 mg/kg) and of scopolamine (0.8 mg/kg) produced a far greater place navigation deficit than scopolamine (0.8 mg/kg) alone. Pilocarpine (pilo) (6.0 mg/kg) reversed the impairment induced by scopolamine (0.8 mg/kg) alone, but the impairment induced by a combination of scopolamine (0.8 mg/kg) and alaproclate (20 mg/kg) was only partially reversed. In visible platform experiment the administration of scopolamine (0.8 mg/kg) did not impair performance, but alaproclate (20 mg/kg) impaired acquisition. Scopolamine (0.8 mg/kg) did not augment alaproclate-induced deficit in visible platform version of the task. In conclusion, we suggest that pharmacological modulation of serotonergic and cholinergic systems affects spatial navigation by modulating different mechanisms underlying different navigation strategies.