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

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 in mice. Both FG 7142 (5 mg/kg) and dizocilpine (0.1 mg/kg) increased the latency to reach shock-free zone (SFZ) both during training and retention session 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 transfer latency (TL) on both first and second day in elevated plus maze. The 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/kg) 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 avoidance task, the higher dose (0.5 mg/kg) increased the latency to reach SFZ on second day. Olanzapine (0.063, 0.125, 0.25 and 0.5 mg/kg) did not show any per 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 elevated plus maze. Although the precise mechanism of action is unknown, olanzapine might be acting by blocking excessive dopaminergic activity in the prefrontal cortex.