D1 and D2 dopamine receptors contribute to the locomotor response induced by Group II mGluRs activation in the rat nucleus accumbens

Abstract

Whereas the involvement of ionotropic glutamate receptors (iGluRs) in the functional interaction between glutamate and dopamine (DA) systems in the nucleus accumbens (N. Acc.) is well established, the role of metabotropic glutamate receptors (mGluRs) is less clear. This study was thus aimed to investigate the mechanisms involving DA and glutamate systems via mGluRs in the generation of motor activity in rats. Intra-accumbens infusion of the Group II agonist (2S,3S,4S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 25, 50, 100 nmol) increased locomotor activity, whereas the Group I agonist (S)-3,5-dihydroxyphenylglycine (S-3,5-DHPG) at the same doses had no effect. The effects of L-CCG-I were blocked by a selective Group II mGluRs antagonist (2S,3S,4S)-2-methyl-2-(carboxypropyl)glycine (MCCG; 50 nmol). The locomotor stimulant effect induced by L-CCG-I might be partly DA mediated, as it is abolished by a pretreatment with the DA receptor antagonist haloperidol (0.1 mg/kg ip) and potentiated by D-amphetamine systemic injection (0.5 mg/kg sc). Furthermore, selective D1 (SCH 23390; 0.005, 0.01 and 0.02 mg/kg) or D2 (raclopride; 0.05, 0.1 and 0.2 mg/kg) antagonists injected systemically were also effective in decreasing L-CCG-I induced hyperactivity. Taken together, these results demonstrate that stimulation of Group II but not Group I mGluRs contributes to the regulation of motor behavior in the N. Acc. and that this increased activity requires the activation of both D1 and D2 DA receptors.