Abstract
To elucidate the roles of dopamine D 1 and D 2 receptors in mediating striatal Fos protein induction and behavioral sensitization after methamphetamine administration, we examined the effects of the D 1 receptor antagonist SCH 23390 and D 2 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 D 1 receptor-mediated mechanisms are involved in the striatal Fos protein induction associated with behavioral sensitization following exposure to methamphetamine.
Published Version
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