Roles of D1 and D2 dopamine receptor subtypes in mediating the methamphetamine-induced changes in monoamine systems.

Previous studies have demonstrated that the effects of methamphetamine (METH) on dopaminergic and serotonergic systems are likely related to METH-induced increases in dopamine release. The ability of haloperidol to prevent these effects of METH suggests that dopamine receptor activation is involved in mediating these METH actions. The present studies were undertaken to determine what role the dopamine receptor subtype(s) might have in such METH effects. We found that the D1 antagonist, SCH23390, attenuated or blocked the effects of METH on dopaminergic and serotonergic systems, whereas the D2 antagonist, sulpiride, blocked the effects of METH on only the dopaminergic system. The results of the present studies suggest that METH-induced increases in dopaminergic action on both D1 and D2 receptors are associated with the effects of METH on the dopaminergic system. In contrast, dopamine action on D1, but not on D2, receptors appears to be involved in the effects of METH on the serotonergic systems of the neostriatum and the cerebral cortex.