Glutamatergic neurons projecting to the nucleus accumbens can affect motor functions in opposite directions depending on the dopaminergic tone.

1. Intracerebral cannulas were implanted stereotactically into the nucleus accumbens, dorsal striatum or nucleus entopeduncularis of male NMRI mice. 2. Monoamine-depleted mice were injected intracerebrally with the competitive NMDA receptor antagonist AP-5, the non-competitive NMDA antagonist MK-801 or the AMPA-kainate receptor antagonist CNQX. A marked locomotor stimulation was produced when AP-5 was injected into the nucleus accumbens, but not when injected into the dorsal striatum. Likewise, CNQX stimulated locomotor activity when injected into the nucleus accumbens. Neither AP-5 nor CNQX produced behavioral stimulation following injection into the nucleus entopeduncularis. 3. The tone in the monoaminergic systems influences the potency of competitive and non-competitive NMDA antagonists differently with regard to stimulation of locomotor activity. In the case of the competitive NMDA antagonist AP-5 the potency was higher in monoamine-depleted than in monoaminergically intact mice. In contrast, the potency of the non-competitive NMDA antagonist MK-801 was higher in monoaminergically intact than in monoamine-depleted animals. 4. A unilateral injection of AP-5 into the nucleus accumbens caused the animals to rotate: The rotation was predominantly ipsilateral in monoaminergically intact animals, whereas monoamine-depleted mice rotated exclusively contralaterally. When AP-5 was given to monoamine-depleted mice treated with the D-2 agonist quinpirole the animals rotated ipsilaterally, whereas monoamine-depleted mice treated with the D-1 agonist SKF 38393 still rotated contralaterally after AP-5 treatment. These data show that glutamatergic neurons projecting to the nucleus accumbens can affect behavior in different directions depending on the degree of dopamine D-2 receptor stimulation.