Metabotropic Glutamate Receptors in the Rat Nucleus Accumbens Contribute to Amphetamine-Induced Locomotion1
Abstract
This study examined the role played by metabotropic glutamate receptors in the nucleus accumbens in dopamine agonist-induced locomotion. Rats received microinjections into this nucleus of the selective metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-carboxyphenylglycine, alone or with amphetamine and their locomotor activity was subsequently measured for 2 hr. None of the doses of (RS)-α-methyl-4-carboxyphenylglycine tested (0.025, 0.25, 2.5, or 25 nmol/0.5 μl/side) when administered alone produced effects on locomotion that differed significantly from those observed after saline. However, when co-injected with amphetamine (6.8 nmol [2.5 μg]/side) into the nucleus accumbens, a moderately high dose of (RS)-α-methyl-4-carboxyphenylglycine (25 nmol/side) completely blocked, whereas a lower dose (0.25 nmol/side) potentiated the locomotor effects of amphetamine. (RS)-α-Methyl-4-carboxyphenylglycine (25 nmol/side) also blocked the locomotor-activating effects of apomorphine (32.9 nmol [10 μg]/side), when co-injected with this direct dopamine receptor agonist into the nucleus accumbens. These results suggest that metabotropic glutamate receptors in the nucleus accumbens contribute to amphetamine-induced locomotion and that this contribution may be mediated, at least in part, by metabotropic glutamate receptors expressed by intrinsic nucleus accumbens cells located postsynaptic to dopamine neuron terminals.
Footnotes
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Send reprint requests to: Paul Vezina, Department of Psychiatry, The University of Chicago, 5841 South Maryland Avenue, MC 3077, Chicago, IL 60637.
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↵1 Supported by grants to P.V. from The Brain Research Foundation.
- Abbreviations:
- DA
- dopamine
- NAcc
- nucleus accumbens
- AMPH
- amphetamine
- iGluRs
- ionotropic glutamate receptors
- AMPA
- α-amino-3-hydroxy-5-methyl isoxazole-4-propionic acid
- NMDA
- N-methyl-d-aspartate
- mGluRs
- metabotropic glutamate receptors
- (1S,3R)-ACPD
- 1-aminocyclopentane-trans-1,3-dicarboxylic acid
- (RS)-MCPG
- (RS)-α-methyl-4-carboxyphenylglycine
- ANOVA
- analysis of variance
- DNQX
- 6,7-dinitroquinoxaline-2,3-dione
- GAMS
- γ-d-glutamylaminomethylsulfonate
- GDEE
- l-glutamic acid diethyl ester
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- Received June 25, 1997.
- Accepted September 8, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
