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Vol. 292, Issue 1, 406-414, January 2000

Regulation of Locomotor Activity by Metabotropic Glutamate Receptors in the Nucleus Accumbens and Ventral Tegmental Area1

Chad J. Swanson and Peter W. Kalivas

Department of Physiology and Neuroscience, Medical University of South Carolina, Charleston, South Carolina

Glutamatergic innervation of the ventral tegmental area (VTA) and the nucleus accumbens (NA) regulates locomotor activity. The present study was designed to evaluate the involvement of metabotropic glutamate receptors (mGluRs) in motor activity. Agonists selective for each of the three subgroups of mGluRs were microinjected into the VTA or NA, and motor activity was monitored. The group I agonist (S)-3,5-dihydroxyphenylglycine elicited a dose-dependent elevation in motor activity after microinjection into either the VTA or NA. The effect in the NA was blocked by the mGluR1-specific antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. The group II agonist (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine also elicited a short-duration motor activation after microinjection into either structure. The dose response in the VTA was biphasic, and the coadministration of the group II/III-specific antagonist (RS)-alpha -methyl-4-phosphonophenylglycine partially blocked motor activation in both the NA and VTA. Although the group III agonist L-(+)-2-amino-4-phosphonobutyric acid produced a relatively modest behavioral stimulation after microinjection into the NA, it was without effect in the VTA. These data indicate a role for mGluR subgroups in the regulation of motor activity in the VTA and NA.

1 This work was supported in part by United States Public Health Service Grants MH-40817 and DA-03906.

0022-3565/0/2921-0406$03.00/0
THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


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