Animal models for tardive dyskinesia: effects of thioridazine

After repeated administration of classical neuroloptics to the rat, supersensitivity of striatal dopamine (DA) receptors towards DA-receptor agonists can be demonstrated. This effect can be quantified (a) by measuring the turning response to apomorphine in rats with unilateral striatal lesions or (b) by measuring the changes induced by neuroleptics in the DA metabolism in the striatum of intact rats. In these test systems, thioridazine induces an increase in DA-receptor sensitivity which is significantly less intense and of shorter duration than that induced by haloperidol. The tendency of a drug to increase DA-receptor sensitivity has been related to its propensity to induce tardive dyskinesia in man, and on this basis it may be expected that tardive dyskinesias following treatment with thioridazine will be rare and less intense than those seen after classical neuroleptics.