OX₂ receptors modulate dopamine efflux in nucleus accumbens in a rat chronic inflammatory pain model

Abstract

The nucleus accumbens (NAc) is a major terminal area for mesocorticolimbic dopamine (DA) projections from the ventral tegmental area. We have reported that focal injection of MK-4305, an OX₁ and OX₂ receptor (-R) antagonist, into the NAc enhanced accumbal DA efflux of rats and that this MK-4305-induced enhancement of DA efflux was inhibited by co-administration of orexin-B, a selective OX₂-R agonist (Kawashima et al., 2022). We also reported that intra-accumbal infusion of MK-4305 induced smaller increases in accumbal DA efflux in rats with intra-planter injection of carrageenan (CAR), a compound that provokes inflammatory pain, relative to injection of vehicle. Here, we examine (a) whether CAR treatment influences basal accumbal DA levels, and (b) the effects of intra-accumbal infusion of orexin-B on MK-4305-induced DA efflux in CAR-treated rats using in vivo microdialysis. Male Sprague-Dawley rats weighing approximately 200 g were used. The doses indicated are the total amounts infused locally into the NAc for 60 min. No significant differences in basal accumbal DA levels were found between rats treated with CAR and those treated with vehicle. Infusion of orexin-B (5 ng), which did not affect basal accumbal DA levels, inhibited the MK-4305 (50 ng)-induced increase in DA efflux in CAR-treated rats. Our findings indicate that (a) CAR-induced inflammatory pain fails to affect basal accumbal DAergic neural activity, and (b) the OX₂-R mediates MK-4305-induced DA efflux in NAc in this rat chronic inflammatory pain model.