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)-alpha-methyl-4-carboxyphenylglycine, alone or with amphetamine and their locomotor activity was subsequently measured for 2 hr. None of the doses of (RS)-alpha-methyl-4-carboxyphenylglycine tested (0.025, 0.25, 2.5, or 25 nmol/0.5 microliter/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 micrograms]/side) into the nucleus accumbens, a moderately high dose of (RS)-alpha-methyl-4-carboxyphenylglycine (25 nmol/side) completely blocked, whereas a lower dose (0.25 nmol/side) potentiated the locomotor effects of amphetamine. (RS)-alpha-Methyl-4-carboxyphenylglycine (25 nmol/side) also blocked the locomotor-activating effects of apomorphine (32.9 nmol [10 micrograms]/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.