Effects of olanzapine and other antipsychotic agents on responding maintained by a conflict schedule

The effects of the “atypical” antipsychotic olanzapine and several other antipsychotics were examined using a conflict schedule. Rats were trained to respond for food on a three-component schedule, comprising variable-interval 30 s (food, VI30) and fixed-ratio 10 s (food + shock, FR10) components separated by time-out (TO). Olanzapine (0.3125–1.25 mg/kg), clozapine (1.25–5 mg/kg) and chlordiazepoxide (2.5–5 mg/kg) decreased or had no effect on VI30 responding, whereas responding in the FR10 component increased. Chlordiazepoxide (5 mg/kg) also increased TO responding. The antipsychotic agents haloperidol (0.125 and 0.25 mg/kg), trifluoperazine (0.0625–0.25 mg/kg), remoxipride (1.25–5 mg/kg) and risperidone (0.0625–0.5 mg/kg) decreased VI30 responding and either had no effect, or decreased TO and FR10 rates. The anticholinergic agent scopolamine (0.03125–0.25 mg/kg) decreased VI30 responding. The 5-HT2 antagonist ritanserin (2.5 and 5 mg/kg) and the anticholinergic agent trihexyphenidyl (2.5 and 5 mg/kg) had no effect on responding. Flumezanil (10 mg/kg) reduced the anticonflict effect of chlordiazepoxide but not olanzapine. These results further emphasize the unusual profile of olanzapine.