Vol. 284, Issue 1, 317-322, 1998

Metabotropic Glutamate Receptors in the Rat Nucleus Accumbens Contribute to Amphetamine-Induced Locomotion¹

Jeong-Hoon Kim and Paul Vezina

Department of Psychiatry, The University of Chicago, Chicago, Illinois

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)--methyl-4-carboxyphenylglycine, alone or with amphetamine and their locomotor activity was subsequently measured for 2 hr. None of the doses of (RS)--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)--methyl-4-carboxyphenylglycine (25 nmol/side) completely blocked, whereas a lower dose (0.25 nmol/side) potentiated the locomotor effects of amphetamine. (RS)--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.