Dopamine D₁ and D₂ receptor antagonism differentially modulates stimulation of striatal neurotransmitter levels by N-methyl-D-aspartic acid

The effects of local perfusion with the dopamine D₁ receptor antagonist SCH 23390 and the dopamine D₂ receptor antagonist raclopride on basal and N-methyl-D-aspartate (NMDA) stimulated dopamine, γ-aminobutyric acid (GABA) and glutamate levels in the dorsolateral striatum were monitored using in vivo microdialysis anaesthetized rat. Local perfusion (90 min) with SCH 23390 and raclopride (1 and 10 μM) dose dependently increased basal striatal dopamine release whereas GABA and glutamate dialysate levels were unaffected. Local perfusion (10 min) with the 1 mM concentration of NMDA increased striatal dopamine, GABA and glutamate outflow. However, when perfused together with SCH 23390 (1 μM) NMDA inhibited glutamate efflux. Moreover, in the presence of SCH 23390 (10 μM) the NMDA induced rise in dopamine and GABA levels was partly prevented. On the other hand, raclopride 1 μM enhanced the NMDA stimulated GABA efflux while at 10 μM it partly counteracted the NMDA induced dopamine release. These data demonstrate that NMDA induced changes in striatal neurotransmitter outflow are effectively modified by dopamine D₁ and D₂ receptor blockade.