Role of dopaminergic mechanisms in the stimulatory effects of MK-801 injected into the ventral tegmental area and the nucleus accumbens

The bilateral administration of 10 mu g of (+)MK-801, but not (-)MK-801, into either the VTA or the N.Ac. stimulated locomotor activity. The stimulation induced by (+)MK-801 at both sites was inhibited by reserpine (5 mg/kg, SC) and the D-1 antagonist, SCH 23390 (0.1 mg/kg, SC). Eticlopride (0.03 mg/kg, SC), a D-2 antagonist, inhibited the stimulation produced by MK-801 in the VTA but not in the N.Ac. Baclofen (32 ng), a GABA(B) receptor agonist, injected into the VTA inhibited the stimulatory response to MK-801 injected systemically, into the VTA, or into the N.Ac., but did not significantly inhibit spontaneous locomotion or the stimulatory response to apomorphine (5 mg/kg, SC). These observations suggest that the stimulatory effects of MK-801 in the VTA and the N.Ac. are dependent on endogenous dopamine. In addition, the effects produced by MK-801 injected into the VTA closely resemble those produced by the systemic administration of low doses of MK-801, suggesting that this is the primary site of action of MK-801.