Microinfusion of the Metabotropic Glutamate Receptor Agonist 1S, 3R–1‐Aminocyclopentane‐1, 3‐dicarboxylic Acid Into the Nucleus Accumbens Induces Dopamine‐dependent Locomotor Activation in the Rat

Abstract

Although the striatum has one of the highest densities of metabotropic glutamate receptor (mGluR) binding sites in the brain, little is known about their physiological role. In this study we characterized the contribution of mGluRs located in the ventral part of the striatum (the nucleus accumbens) to the control of extrapyramidal motor function. Activation of mGluRs by local infusion of the selective agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 25, 50 and 100 nmol/0.5 microl) into the nucleus accumbens induced a dose-dependent increase in locomotor activity in rats. Intra-accumbens infusion of a selective antagonist of mGluRs, alpha-methyl-4-carboxyphenylglycine (MCPG) did not modify spontaneous locomotion but decreased the locomotor response to 1S,3R-ACPD. This effect appeared to be mediated by dopamine, since blockade of dopamine receptors with haloperidol (0.05 and 0.1 mg/kg i.p.) dose-dependently reduced 1S,3R-ACPD-induced locomotor activation. Furthermore, D-amphetamine (0.5 mg/kg, i.p.) combined with intra-accumbens infusion of 1S,3R-ACPD (100 nmol) potentiated the locomotor hyperactivity response to a higher level than that seen with a single treatment with either drug. In contrast, D-amphetamine-induced hypermotility was abolished by infusion of MCPG (100 nmol) into the nucleus accumbens. These results demonstrate that glutamate may control extrapyramidal motor function through metabotropic receptors. Furthermore, activation of metabotropic glutamate receptors appears to act in synergy with the dopamine system at the level of the nucleus accumbens to produce a motor stimulant response.