The pathophysiology of tardive dyskinesia.

In rodent models of tardive dyskinesia, dopamine-agonist-induced stereotyped behaviors after neuroleptic administration are used to assess presumed striatal postsynaptic receptor hypersensitivity. Early studies provided evidence that neuroleptic pretreatment did alter dopaminergic receptor sensitivity and hence the threshold for amine-induced stereotyped behavior. Later studies showed a dose effect for several neuroleptics. However, no hypersensitivity was seen with thioridazine, which prevented or reversed haloperidol-induced hypersensitivity. Duration appeared to be a risk factor early in but not throughout neuroleptic administration. These findings may have implications for the understanding and prevention of tardive dyskinesia in man.