Stimulation of dopamine D2 receptors in the nucleus accumbens inhibits inflammatory pain.

Previous studies suggest that dopamine in the nucleus accumbens links noxious or mesolimbic stimulation with the feedback inhibition of nociception. To test the hypothesis that pharmacological agonism at dopamine receptors in the nucleus accumbens elicits antinociception, we bilaterally microinjected dopamine D1- and D2-receptor subtype selective drugs, and then evaluated behavioral responses to noxious intraplantar formalin. While the D1-selective agonist SKF 38393 was without effect at a dose of 0.5 nmol/side, the D2-selective agonist quinpirole dose-dependently (0.05-5.0 nmol/side, bilateral) inhibited the persistent phase of formalin-induced nociception. This was blocked by pre-administration of a selective D2-dopaminergic antagonist raclopride (0.3 nmol/side, bilateral). Quinpirole did not produce overt behavioral effects and did not change rotarod latency. Our results indicate that quinpirole acts at dopamine D2 receptors in the nucleus accumbens to inhibit persistent nociception at doses that circumvent confounding non-specific motor deficits, namely, sedation and motor coordination.