Protection against acute amphetamine-induced behavior by microinjection of a group II metabotropic glutamate receptor agonist into the dorsal striatum of rats

Abstract

Group II metabotropic glutamate receptors (mGluRs) are distributed both pre- and postsynaptically in the striatum. By bilaterally administering a subgroup-selective agonist or antagonist into the dorsal striatum of chronically cannulated rats, this study examined the role of striatal group II mGluRs in the regulation of basal and dopamine-stimulated motor behavior. Intrastriatal injection of a group II agonist, (2S,2′R,3′R)-2-(2′,3′-dicarboxycyclopropyl)glycine (DCG-IV, 0.01, 0.1 and 1 nmol), dose-dependently reduced basal levels of motor activity. Pretreatment of rats with intrastriatal DCG-IV at a higher dose (1 nmol), but not a lower dose (0.01 nmol), produced complete or partial blockade of hyperlocomotion induced by acute injection of amphetamine (2.5 mg/kg, i.p.) or apomorphine (1 mg/kg, s.c.), respectively. Blockade of group II mGluRs by intrastriatal injection of a group II antagonist, (RS)-α-methylserine-O-phosphate monophenyl ester (10 nmol), was found to: (i) induce a moderate locomotion by itself; (ii) augment amphetamine-stimulated behaviors and (iii) attenuate DCG-IV-induced reduction of basal and amphetamine-stimulated motor activity. These data demonstrate that the group II mGluRs in the striatum play a significant role in the inhibitory modulation of tonic and phasic motor activity, which is most likely processed through both pre- and postsynaptic mechanisms.