Possible genetic factors underlying the pathophysiology of tardive dyskinesia

Rates of spontaneous and drug-induced repetitive jaw movements (RJM) in rats vary widely. Low and high RJM responders were isolated and genetically selected. At each generation mean RJM responses (spontaneous or SKF 38393-induced) of the two types of rats were found to differ significantly, whereas neither apomorphine-induced stereotypic responses nor D1 and D2 receptor numbers and affinities differed. A significant increase in cAMP production was evident in SKF 38393-stimulated striatal homogenates of high RJM responders as compared with low responders. Animals subjected to 8-months exposure to fluphenazine exhibited RJM that were about twice as great as that of controls, 2 months after the last treatment, with a prevalence of about 75%. Similarities between RJM observed in rats and neuroleptic-induced tardive dyskinesia suggest that the two are strongly related.