Effects of THA and physostigmine on spatial navigation and avoidance performance in mecamylamine and PCPA-treated...

The present study compares the effects of two cholinesterase inhibitors, tetrahydroaminoacridine (THA, 1 and 3 mg/kg) and physostigmine (0.12 and 0.36 mg/kg), on spatial navigation (water maze, WM) and avoidance (step through passive avoidance, PA) performance. THA and physostigmine did not facilitate WM or PA performance in control or p-chlorophenylalanine (PCPA)-treated rats. THA at 3 mg/kg, but not at 1 mg/kg, completely restored the defect in WM and PA performance in rats pretreated with 7.5 mg/kg mecamylamine, a centrally active nicotinic antagonist. Physostigmine completely restored behavior in WM and PA tests at 0.12 and 0.36 mg/kg in mecamylamine-treated rats. In rats pretreated with mecamylamine+PCPA, 3 mg/kg THA to some extent restored WM performance but had no effect on PA retention. Likewise, physostigmine partially restored WM performance but did not facilitate PA retention in mecamylamine+PCPA-pretreated rats. The present study suggests that serotonergic dysfunction may decrease the efficacy of cholinesterase inhibitors to reverse the defect in WM and PA behavior occurring as a consequence of a decrease in activity of nicotinic-mediated functions.