The effects of olanzapine, clozapine, and haloperidol on vacuous jaw movements and psychotomimetic-induced behaviors in the rat

Olanzapine is a potential atypical antipsychotic which received Food and Drug Administration approval on September 30, 1996. The purpose of the present research project was to determine the behavioral profile of olanzapine in a rodent model of atypicality. Experiment 1 investigated the effects of acute and chronic olanzapine administration on vacuous jaw movements, as a screening procedure for risk of extrapyramidal side effects. The ability of olanzapine to reverse phencyclidine-induced social withdrawal, which is an index of negative symptomatology, was assessed in Experiment 2 using the tether paradigm developed in our laboratory. Of note, the behavioral effects of olanzapine were compared to haloperidol and clozapine in both experiments. Consistent with previous findings, the results of Experiment 1 revealed that acute administration of haloperidol produced a greater number of vacuous jaw movements than olanzapine and clozapine. Furthermore, chronic administration of haloperidol also resulted in greater vacuous jaw movements compared to clozapine. However, chronic administration of olanzapine produced greater vacuous jaw movements than both haloperidol and clozapine. As found in previous studies, the results of Experiment 2 indicated that phencyclidine administration generally decreased social interaction. In addition, the effects of each antipsychotic alone on social behavior were variable. Specifically, administration of clozapine and olanzapine produced a trend toward a decrease in social interaction. On the other hand, haloperidol produced a significant increase in social interaction following administration of the highest dose (0.3 mg/kg). Finally, haloperidol, clozapine, and olanzapine were able to partially restore the time spent in contact toward baseline levels of social interaction. Haloperidol and olanzapine were also able to partially restore the number of contacts toward baseline levels of social interaction, while clozapine administration had no effect on this measure. In conclusion, olanzapine and haloperidol administration resulted in increased vacuous jaw movements, while clozapine administration did not. Haloperidol, clozapine, and olanzapine produced a non-significant trend towards reversing phencyclidine-induced social withdrawal. These findings are discussed in the context of mesolimbic/mesocortical specificity versus nigrostriatal specificity and dose ranges employed for each antipsychotic.