Study on the suitability of a rat model for tardive dyskinesia and the preventive effects of various drugs

1. Male Sprague-Dawley rats (weighing 260-300 g) were administered 1.5 mg/kg of haloperidol (HPD) intraperitoneally once daily for 28 days to produce an animal model for tardive dyskinesia (TD). The daily administration of HPD significantly increased the frequency of involuntary orofacial movements (chewing movements, tongue protrusions and buccal tremors). 2. Its suitability as a model for TD was assessed in terms of the therapeutic effects of 6 drugs trihexyphenodyl hydrochloride(THP), clonazepam(CZP), sodium valproate(VPA), alpha-tocopherol(Vit E), ritanserin(RS) and propranolol hydrochloride(PPL)]. These drugs were also used concomitantly with HPD to study their preventive effect. 3. As for the therapeutic effects of the drugs, both the single and the 14-day daily administrations of CZP as well as of VPA significantly suppressed the chewing movements. The results were mostly consistent with the effect of each drug on human TD, indicating this would be an excellent model for TD in terms of the drug responsiveness. 4. The concomitant administration of RS from the start of HPD administration significantly suppressed the appearance of chewing movements. The concomitant administration of Vit E for 42 days also suppressed chewing movements and buccal tremors. On the other hand, the concomitant administration of THP tended to aggravate these involuntary movements. 5. The fact that the therapeutic and preventive effects of the drugs on this model differed suggested that the development and recovery of the movements might also differ, at least in part.