Nucleus accumbens NMDA antagonist decreases locomotor activity produced by cocaine, heroin or accumbens dopamine, but not caffeine

Glutamatergic afferents to the nucleus accumbens (NAC) have been suggested to modulate psychostimulant-induced locomotor activation. The purpose of this study was 1) to determine the importance of nucleus accumbens N-methyl-D-aspartate (NMDA) glutamate receptors in the control of psychostimulant-induced locomotion, 2) to determine whether NMDA receptor modulation of psychostimulant-induced locomotion occurs presynaptic to or postsynaptic to NAC dopamine terminals, and 3) to determine whether NMDA receptors also modulate opiate- and caffeine-induced locomotor activation. For this purpose, rats treated with cocaine (10 mg/kg IP), dopamine (20 micrograms directly into the NAC), heroin (0.5 mg/kg SC), or caffeine (10 mg/kg SC) were challenged with intra-NAC microinfusion of 2-amino-5-phosphonovaleric acid (APV), a selective NMDA receptor antagonist. APV reduced locomotor activation induced by cocaine, heroin and intra-NAC dopamine, but not caffeine. These results suggest that NAC glutamate modulates psychomotor stimulation at the level of the NAC through an interaction with the integrated output of this region.