Activation of metabotropic glutamate receptors in the rat nucleus accumbens increases locomotor activity in a dopamine-dependent manner.

The effect on locomotor activity of in vivo activation of metabotropic glutamate receptors (mGluRs) in the nucleus accumbens (NAcc) was investigated in rats. Bilateral intracranial microinjections into the NAcc of the selective mGluR agonist, 1-aminocyclopentane-trans-1,3-dicarboxylic acid [(1S,3R)-ACPD], were made in the freely moving rat and locomotor activity was subsequently measured for 2 hr. Different groups of rats injected with one of four doses of (1S,3R)-ACPD (0.005, 0.05, 0.5, or 2.5 nmol/0.5 microl/side) showed significant dose-dependent increases in both horizontal and vertical locomotor activity relative to control rats that received injections of the saline vehicle. Time-course analyses revealed that these effects, in a manner similar to the locomotor hyperactivity produced by the injection of amphetamine into the NAcc, were most pronounced in the initial 30 min after injection and no longer present after 1 hr of testing. These locomotor-activating effects of (1S,3R)-ACPD were blocked by the co-injection of the mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (2.5 nmol/side), as well as of the dopamine receptor antagonist, fluphenazine (2.0 or 9.8 nmol/side), which suggests that they depend on dopamine neurotransmission. These findings indicate that mGluRs play an important role in the production of locomotor behaviors involving DA-excitatory amino acid interactions in the NAcc.