Abstract

Introduction

The Locomotion Produced by Activation of NAcc mGluRs is DA-Dependent

NAcc mGluRs Contribute to AMPH-Induced Locomotion

NAcc mGluRs and the Expression of Locomotor Sensitization by AMPH

Summary and References

Discussion
Board

Interactions between excitatory amino acids and dopamine (DA) in the basal ganglia have been known for some time to contribute importantly to the generation of motor behaviors. Results are presented that support an important role for interactions between nucleus accumbens (NAcc) DA and metabotropic glutamate receptors (mGluR) in the generation of locomotion. Bilateral infusions into the rat NAcc of the mGluR agonist (1S,3R)-ACPD (0.005-2.5 nmole/side) dose-dependently increased locomotion. This increase was blocked by 6-OHDA lesions of DA terminals in the NAcc or by co-injections of the mGluR antagonist (RS)-MCPG or the DA receptor antagonist fluphenazine. Co-injection of a dose of (RS)-MCPG that was without locomotor effects of its own completely blocked the increased locomotion produced by either NAcc amphetamine or apomorphine. This latter effect of (RS)-MCPG on NAcc amphetamine-induced locomotion appeared to be due to group II, but not group I, mGluRs since it was mimicked by the group II mGluR antagonist EGLU but not by equimolar doses of the group I mGluR antagonist AIDA. Finally, NAcc (RS)-MCPG, which had no effect on locomotion when given to saline pre-exposed rats, produced significant increases in locomotion when administered to amphetamine pre-exposed rats, suggesting that glutamatergic neurotransmission mediated by NAcc mGluRs is altered by repeated systemic injections of amphetamine. Together, these results support a role for NAcc DA and mGluR interactions in the generation of locomotion and at least one form of plasticity: the sensitization of locomotor activity by psychomotor stimulant drugs.

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Presentation Number SAvezina0407
Keywords: glutamate, dopamine, locomotion, nucleus accumbens, sensitization