Effect of olanzapine on behavioural changes induced by FG 7142 and dizocilpine on active avoidance and plus maze tasks

The present study examined the effect of atypical antipsychotic olanzapine on FG 7142- (N-methyl-beta-carboline-3-carboxamide) and dizocilpine-induced cognitive impairment in active avoidance paradigm and elevated plus maze i n mice. Both FG 7142 (5 mg/kg) and dizocilpine (0.1 mg/kg) increased the la tency to reach shock-free zone (SFZ) both during training and retention ses sion in active avoidance paradigm. This effect was reversed by olanzapine ( 0.063, 0.125, 0.25 and 0.5 mg/kg). Similarly, FG 7142 (5 mg/kg) increased t ransfer latency (TL) on both first and second day in elevated plus maze. Th e lower doses of olanzapine (0.063 and 0.125 mg/kg) reversed the effect of FG 7142 on second day in elevated plus maze but higher doses (0.25 and 0.5 mg/kg) failed to modify the effect of FG 7142 both on first and second day. Dizocilpine (0.1 mg/kg) treatment did not affect TL on first day while on second day, it increased TL significantly. Olanzapine (0.063 and 0.125 mg/k g) reversed the effect of dizocilpine on elevated plus maze but the higher doses (0.25 and 0.5 mg/kg) failed to reverse it. Even though olanzapine (0. 063, 0.125 and 0.25 mg/kg) failed show any effect per se in active avoidanc e task, the higher dose (0.5 mg/kg) increased the latency to reach SFZ on s econd day. Olanzapine (0.063, 0.125, 0.25 and 0.5 mg/kg) did not show any p er se effect on TL in elevated plus maze on first day while on second day, olanzapine (0.125, 0.25 and 0.5 mg/kg) increased TL as compared to control group. The present study demonstrated olanzapine's reversal of dizocilpine- and FG 7142-induced behavioural changes in active avoidance paradigm and e levated plus maze. Although the precise mechanism of action is unknown, ola nzapine might be acting by blocking excessive dopaminergic activity in the prefrontal cortex. (C) 1999 Elsevier Science B.V. All rights reserved.