Involvement of orexin-1 receptors in the ventral tegmental area and the nucleus accumbens in antinociception induced by lateral hypothalamus stimulation in rats

Previous studies have demonstrated that chemical stimulation of the lateral hypothalamus (LH) with carbachol has an important role in the induction of antinociception in tail-flick test as a model of acute pain. In this study, we tried to evaluate the involvement of orexin-1 receptors in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) on antinociceptive responses induced by LH stimulation in rats. One hundred twenty adult male albino Wistar rats weighing 200-250 g were unilaterally implanted with two separate cannulae into the LH, and VTA or NAc. Antinociceptive effects for two doses of intra-LH carbachol (125 and 250 nmol/0.5 μl saline), as a cholinergic agonist, were evaluated in this study. In another set of experiments, animals received intra-VTA or -NAc infusions of SB334867 as a selective orexin-A receptor antagonist (0.3, 1, 3 and 10 nmol/rat), just 5 min before microinjection of an effective dose of carbachol into the LH. In the tail-flick test, antinociceptive responses of drugs were obtained by tail-flick analgesiometer and represented as maximal possible effects (%MPE) at 5, 15, 30, 45 and 60 min after their administrations. The results showed that unilateral intra-LH administration of carbachol (125 and 250 nmol/rat) induced antinociception in rats (P < 0.01). There were no significant differences between the antinociceptive effects of these two doses. In the second part of our study, intra-VTA and intra-accumbal administrations of different doses of SB334867, 5 min before microinjection of carbachol, could dose-dependently prevent the development of LH stimulation-induced antinociception in rats. However, this effect was less in the NAc. It is supposed that the orexinergic projections from the LH to the VTA and NAc are direct/indirectly involved in the antinociception induced by LH chemical stimulation, and orexin-1 receptors in the ventral tegmental area have a more substantial role in this phenomenon.