Oral administration of haloperidol at clinically recommended doses elicits smaller parkinsonian effects but more tardive dyskinesia in rats

The present study was designed to monitor extrapyramidal symptoms (EPS) elicited by the oral administration of haloperidol at clinically recommended doses and to compare it with EPS produced when the drug is injected intraperitoneally at doses used in animal research. Rats injected with haloperidol at a dose of 1 mg/kg daily for 5 weeks exhibited akinesia in an open field and impaired motor coordination. Effects of the drug on motor coordination but not on open field akinesia were attenuated gradually from 2-5 weeks of treatment. Oral administration of haloperidol in drinking water at clinically recommended dose exhibited decreased exploratory activity without producing akinesia. Motor coordination was impaired maximally after 3 weeks and tolerance was developed in the drug induced motor impairment after 5 weeks of treatment. Intensity of vacuous chewing movements (VCMs) and tardive VCMs was greater by oral administration than intraperitoneal injections of haloperidol. The present results showed that oral administration of haloperidol expected to produce sustained effect may result in tolerance in acute parkinsonian like effects but more intensity of tardive dyskinesia. We suggest that drugs which may helpful in alleviating tardive dyskinesia may be more useful if person is on oral drug therapy.