Induction of locomotor activity by the glutamate antagonist DNQX injected into the ventral tegmental area

Abstract

DNQX, an antagonist of AMPA/kainate receptors, was injected into the ventral tegmental area (VTA) to test the hypothesis that AMPA/kainate receptors in this brain region might be involved in regulation of locomotor activity. Bilateral injection of 1 μg DNQX into the VTA increased locomotor activity. In addition, unilateral injection of DNQX into this site produced contraversive turning, which was potentiated by coadministration of amphetamine (1 mg/kg, i.p.). These results suggest that a glutamatergic afferent to the VTA is tonically active in inhibiting locomotor activity. The locomotor stimulation produced by DNQX was not associated with a change in DOPAC/DA level in the nucleus accumbens or the striatum. However, the locomotor stimulation produced by DNQX was markedly attenuated following blockade of dopaminergic receptors by haloperidol (0.5 mg/kg, s.c.) or following dopamine depletion induced by reserpine plus α-methyl- para -tyrosine pretreatment. These results suggest that a basal activation of dopaminergic receptors is required for expression of the locomotor activity elicited by DNQX.