Dopaminergic supersensitivity after long-term administration of phenytoin in rats.

Male albino rats (n = 10) were injected with phenytoin (PHT) every day for 20 consecutive days and were tested on days 21 and 28 for their response to 1 mg/kg apomorphine, a dopamine-receptor agonist. Rats treated with PHT showed an increased responsiveness to apomorphine-induced stereotypy on day 28, which is evidence for dopaminergic supersensitivity after long-term treatment with the drug. In experiment 2, a supersensitivity response to apomorphine-induced stereotypy was noted on day 14 after 10 days of PHT administration. In experiment 3, after 17 days of PHT administration, rats were also supersensitive to the climbing response induced by apomorphine. These results may explain, in part, the clinical findings of orofacial dyskinesias produced by PHT in epileptic patients.