The role of dopamine receptors in ventrolateral orbital cortex-evoked antinociception in a rat formalin test model

The present study examined the roles of dopamine and D1- and D2-like dopamine receptors in ventrolateral orbital cortex (VLO)-evoked antinociception in rats with persistent inflammatory pain. Following formalin injection into the rat unilateral hindpaw pad, the effects of dopamine receptor agonist and antagonist microinjections into the VLO on nociceptive behavior were observed. Results demonstrated that VLO microinjection of the non-selective dopamine receptor agonist apomorphine (R(−)-apomorphine hydrochloride, 1.0, 2.5 and 5.0 μg) depressed later-phase nociceptive behavior induced by formalin injection; this effect was attenuated by the D2-like dopamine receptor antagonist S(−)-raclopride(+)-tartrate salt (raclopride, 3.0 μg), but not by the D1-like dopamine receptor antagonist R(+)-SCH-23390 hydrochloride (SCH-23390, 1.0 μg). Apomorphine-induced antinociception was mimicked by microinjection of the D2-like dopamine receptor agonist (−)-quinpirole hydrochloride (2.0 and 5.0 μg) into the same VLO site, and this effect was antagonized by raclopride (3.0 μg). In addition, microinjection of the D1-like dopamine receptor agonist R(+)-SKF-38393 hydrochloride (5.0 μg) had no effect on formalin-induced nociceptive behavior during the later phase. However, the D1-like dopamine receptor antagonist SCH-23390 (2.5, 5.0 and 10 μg) depressed nociceptive behavior in a dose-dependent manner. These results suggested that dopamine mediated VLO-induced antinociception via different mechanisms in the persistent inflammatory pain model; D2-like receptors mediated dopamine-induced antinociception, while D1-like dopamine receptors exhibited tonic facilitatory action on nociceptive behavior, thereby blocking D1-like dopamine receptors could induce antinociception.