Metabotropic glutamate receptors in the rat nucleus accumbens contribute to amphetamine-induced locomotion.
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.
Kim
J H
JH
Department of Psychiatry, University of Chicago, Illinois, USA.
Vezina
P
P
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*
D001565:Benzoates; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; C079694:alpha-methyl-4-carboxyphenylglycine; D000661:Amphetamine; D005998:Glycine