Excitatory amino acids and picrotoxin have been shown to produce an intense stimulation of co-ordinated locomotor activity after bilateral administration into the nucleus accumbens of rats. The objective of this study was to determine the role of GABAergic neurotransmission in t he substantia innominata/lateral preoptic area in the hypermotility responses to excitatory amino acids and picrotoxin. It was found that the bilateral administration of muscimol into the substantia innominata/lateral preoptic area almost completely inhibited the stimulation of locomotor activity induced by the administration of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), kainic acid, N-methyl-D-aspartic acid and picrotoxin into the n. accumbens. In contrast, muscimol did not inhibit locomotor activity or induce catalepsy in control animals injected with saline into the nucleus accumbens. The inhibitory effect of muscimol on the hypermotility responses to excitatory amino acids and picrotoxin was not due to diffusion to the nucleus accumbens and the activation of GABAergic receptors at this site. This conclusion is preoptic area, which effectively inhibited the responses to AMPA and picrotoxin, were either much less effective or not effective in inhibiting these responses when injected into the nucleus accumbens. These observations suggest that the stimulation of locomotor activity produced by the injection of excitatory amino acids or picrotoxin into the nucleus accumbens may be mediated by the inhibition of a GABAergic neuronal pathway projecting from the nucleus accumbens to the substantia innominata/lateral preoptic area.