Methamphetamine-Induced Sensitization of Dopamine Release via a Metabotropic Glutamate Receptor Mediated Pathway in Rat Striatal Slices

Abstract

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. transACPD-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.