Stimulatory effect of N-methyl aspartate on locomotor activity and transmitter release from rat nucleus accumbens.

N-Methyl-aspartate (NMA), an agonist at central glutamate receptors, elicited prolonged and intense locomotor activity when injected into the nucleus accumbens septi (NAS) in subconvulsive doses (3-10 micrograms bilaterally). This effect was antagonised by intra-accumbens injection of the specific NMA antagonist, aminophosphonovaleric acid (APV) in a dose (3.0 micrograms bilaterally) that was without intrinsic effect when given on its own. Intra-accumbens injection of APV also suppressed locomotor hyperactivity elicited by intra-accumbens injection of DA (50 micrograms bilaterally) in rats pretreated with nialamide. In vitro release of [3H]-acetylcholine in accumbens tissue slices was significantly increased in the presence of NMA (30 microM) or N-methyl-D-aspartate (NMDA) (15 microM). Both effects were antagonised by APV (30 microM). Similar results were obtained with tissue slices of rat corpus striatum. These results suggest that locomotor stimulation by intra-accumbens NMA is mediated by an action on the mesolimbic dopaminergic neuron, either directly or via a cholinergic interneuron. In addition, activity at the glutamate synapse may be enhanced by the presence of DA affecting glutamate release and/or reuptake.