To test the hypothesis that the
motor hyperactivity associated with intra-accumbens
injections of
N-methyl-d-aspartate (
NMDA) results from stimulation (direct or indirect) of nucleus accumbens dopaminergic mechanisms, the behavioral effects of intra-accumbens and intraventricular
NMDA were compared to those of the prototypic dopaminergic releasing agent,
amphetamine, and the competitive
NMDA receptor antagonist,
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (
CPP). Drugs were injected into the right lateral ventricle, or bilaterally into the nucleus accumbens of rats. Locomotor activity was monitored electronically and by direct observation for 40 min prior to, and 1 hour after,
drug treatment. Intra-accumbens
injections of
NMDA (0.4, 1.2 and 2.0 micrograms/side) produced dose-related increases in distance traveled, but had no significant effect on movement time or vertical movements. The
NMDA-induced increase in distance traveled was temporally correlated with convulsive wild running, but not with exploratory behavior, suggesting that this increase may have been secondary to seizure-like activity. Intra-accumbens
injections of
amphetamine (10, 20 and 40 micrograms) or
CPP (0.1 microgram) produced dose-related increases in all three measures. By the intraventricular route, the effects of
NMDA were similar to those of intra-accumbens administration, whereas intraventricularly administered
d-amphetamine had no effect. The behavioral effects of intra-accumbens
NMDA cannot be explained by an
NMDA receptor-mediated facilitation of dopaminergic neurotransmission; rather, this type of facilitation may be associated with competitive
NMDA receptor antagonism.