Roles of dopamine D1 receptors in striatal fos protein induction associated with methamphetamine behavioral sensitization in rats.

To elucidate the roles of dopamine D1 and D2 receptors in mediating strial Fos protein induction and behavioral sensitization after methamphetamine administration, we examined the effects of the D1 receptor antagonist SCH 23390 and D2 receptor antagonist sulpiride on these phenomena in rats. Intraperitoneal administration of 5.0 mg/kg methamphetamine produced a significant increase in Fos-immunoreactive cells in the medial striatum. Prior exposure to 5.0 mg/kg methamphetamine enhanced ipsilateral rotational behavior in response to subsequent methamphetamine administration in unilateral nigral-lesioned rats (sensitization). Pretreatment with SCH 23390 (0.32 mg/kg IP) suppressed significantly the expression of striatal Fos protein and the development of acute behavioral sensitization following a single injection of 5.0 mg/kg methamphetamine. Sulpiride (50 mg/kg IP) was also effective in suppressing methamphetamine behavioral sensitization, but did not affect the striatal Fos induction. These results suggest that dopamine D1 receptor-mediated mechanisms are involved in the striatal Fos protein induction associated with behavioral sensitization following exposure to methamphetamine.