Orexin A induced antinociception in the ventral tegmental area involves D1 and D2 receptors in the nucleus accumbens

Previous studies have shown that there are functional interactions among the lateral hypothalamus (LH), ventral tegmental area (VTA) and the nucleus accumbens (NAc), implicating pain modulation in the central nervous system. It has been shown that the LH-VTA orexinergic projecting neurons play an important role in mediating the suppression of nociception in animal models. However, little is known about the function of intra-VTA orexin receptors and involvement of D1/D2 receptors within the NAc in this antinociception. In the present study, we investigated the effect of direct administration of orexin A into the VTA, and examined the role of intra-accumbal dopamine receptors in tail-flick test as a model of acute nociceptive responses in rats. Adult male Wistar rats were unilaterally implanted by two separate cannulae into the VTA and NAc. The results showed that intra-VTA orexin A (0.055, 0.55, 5.5 and 55ng/0.3μl saline) could induce antinociception in a dose-dependent manner. In two separated supergroups, rats received intra-accumbal infusions of D1 and D2 receptor antagonists, SCH-23390 and sulpiride (0.125, 0.25, 1 and 4μg/rat) prior to intra-VTA orexin A (5.5ng/rat) administration respectively. Antinociceptive responses of drugs are represented as maximal possible effect in 5, 15, 30, 45 and 60min after their administrations. Our findings showed that intra-accumbal SCH-23390 and sulpiride dose-dependently prevented intra-VTA orexin-induced antinociception. Nevertheless, this effect is more potent in animals that received D2 receptor antagonist. It is supposed that orexin A can induce the antinociception through activation of orexinergic receptors which activate the dopaminergic inputs to the NAc in rats.