We studied the roles of metabotropic glutamate receptors in methamphetamine (MAP)-induced sensitization of dopamine (DA) release from striatal slices. Rats were first treated with MAP (1 mg/kg, i.p.) once daily for 6 consecutive days. After a 6-day withdrawal, DA release from striatal slices evoked by ±-1-aminocyclopentane-trans-1,3-dicarboxylic acid (trans-ACPD) was measured. trans-ACPD-induced DA release was significantly enhanced in MAP-sensitized rats, but the inactive form of trans-ACPD (1R,3S-ACPD) did not enhance DA release. The active form of trans-ACPD (1S,3R-ACPD) (0.1 mM)-evoked DA release was attenuated by treatment with 0.4 mM RS-α-methyl-4-carboxyphenylglycine, a metabotropic glutamate receptor antagonist. The present results suggest that metabotropic glutamate receptors play an important role in expression of MAP-induced sensitization.
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