The effects of cyproheptadine on vacuous jaw movements in rats: a comparison with haloperidol and clozapine.

Classic neuroleptics produce a syndrome of vacuous jaw movements in rats, but atypical neuroleptics such as clozapine do not. This syndrome has been offered as a rapid and inexpensive means of assaying novel antipsychotic compounds for the production of early onset extrapyramidal side effects. Cyproheptadine is a serotonergic antagonist that has been suggested for the treatment of schizophrenia. The present study compared the effects of repeated administration of cyproheptadine with those of the classic antipsychotic haloperidol and the atypical antipsychotic clozapine in terms of their production of vacuous jaw movements. Rats were administered either tartaric acid vehicle or one of three doses of each drug daily for a month. Once a week the rats were observed for a 5-minute period by two trained observers who recorded their vacuous jaw movements. Cyproheptadine produced elevations in vacuous jaw movements similar to those produced by haloperidol, but clozapine did not. These results indicate that cyproheptadine may be similar to classic antipsychotics in the production of extrapyramidal symptoms in humans, and they underscore the usefulness of vacuous jaw movement model of early onset extrapyramidal side effects.