Sensitization of mice to methylphenidate.

Mice that received five daily injection of methylphenidate HCl, 10-75 mg/kg, showed an increased running response to methylphenidate, cocaine, and amphetamine. Sensitization to methylphenidate persisted for at least 50 days. Repeated IP injections of methylphenidate into mice with unilateral striatal lesions increased ipsilateral turning in response to methylphenidate, but decreased contralateral turning after apomorphine. The climbing response to apomorphine in intact, methylphenidate-sensitized mice was also decreased. There was no change in either basal or dopamine-stimulated adenyl cyclase activity in the striata of sensitized mice, but there was a 36% increase in the specific binding of haloperidol. The rate of turnover of striatal dopamine was increased in sensitized mice. These results suggest that pretreatment with methylphenidate may alter the sensitivity of presynaptic dopamine receptors.