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

Group II metabotropic glutamate receptors (mGluRs) are distributed both pre - and postsynaptically in the striatum. By bilaterally administering a subg roup-selective agonist or antagonist into the dorsal striatum of chronicall y cannulated rats, this study examined the role of striatal group II mGluRs ; in the regulation of basal and dopamine-stimulated motor behavior. Intras triatal injection of a group II agonist, (2S,2'R,3'R)-2-(2',3'-dicarboxycyc lopropyl)glycine (DCG-IV, 0.01, 0.1 and 1 nmol), dose-dependently reduced b asal 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 co mplete 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 anta gonist, (RS)-alpha-methylserine-O-phosphate monophenyl ester (10 nmol), was found to: (i) induce a moderate locomotion by itself; (ii) augment ampheta mine-stimulated behaviors and (iii) attenuate DCG-IV-induced reduction of b asal and amphetamine-stimulated motor activity. These data demonstrate that the group II mGluRs in the striatum play a significant role in the inhibit ory modulation of tonic and phasic motor activity, which is most likely pro cessed through both pre- and postsynaptic mechanisms. (C) 1999 Elsevier Sci ence Ireland Ltd. All rights reserved.