The effects of alaproclate and p-chlorophenylalanine on cued navigation performance in rats

The present study investigates the effects of a serotonin (5-HT) reuptake inhibitor, alaproclate, on water maze cued navigation performance in serotonin depleted and control rats. Treatment with p-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, (400 mg/kg/day x 3 i.p.) significantly depleted cerebral levels of both 5-HT (about 80% depletion) and its major metabolite 5-HIAA (about 90% depletion) for at least 7 days. PCPA treatment also slightly decreased cerebral noradrenaline and dopamine levels (16% and 22% reductions, respectively). PCPA treatment alone had no effect on the acquisition of the cued navigation version (visible platform) of the water maze task measured as the distance to find the escape platform, but it significantly increased swimming speeds of the rats. Alaproclate (20 mg/kg i.p.) increased escape distance and slightly decreased swimming speeds of the rats. The effects of alaproclate did not differ between PCPA and sham treated (arabic gum 400 mg/kg/day x 3 i.p.) rats. The results demonstrate that alaproclate induced cued navigation behavioral deficit is maintained after a marked depletion of cerebral serotonin.