Search

Several lines of evidence have shown that stimulation of the lateral hypothalamus (LH) can induce antinociception. It has been indicated that hypothalamic orexinergic neurons send projections throughout the dopamine mesolimbic pathway. Functional interaction between the LH and the main area of the mesolimbic pathway such as the ventral tegmental area (VTA) and the nucleus accumbens (NAc) implicates in pain modulation. Thus, in this study, we investigated the role of D2-like dopamine receptors within the VTA and NAc in the LH stimulation-induced antinociception. Male Wistar rats weighing 230-280 g were unilaterally implanted with two separate cannulae into the LH and VTA or NAc. Animals received intra-VTA (0.25, 1 and 4 μg/0.3 μl DMSO) and intra-accumbal (0.125, 0.25, 1 and 4 μg/0.5 μl DMSO) infusions of sulpiride as a selective D2-like receptor antagonist, prior to intra-LH carbachol (125 nM/rat) administration. In the tail-flick test, the antinociceptive effects were measured using a tail-flick algesiometer and represented as maximal possible effect (%MPE) within 5, 15, 30, 45 and 60 min after injections. Our results showed that intra-VTA and intra-accumbal sulpiride dose-dependently attenuated the LH stimulation-induced antinociception. However, the blockade of D2-like receptors within the NAc was more significant than that of the VTA. These findings show that D2-like dopamine receptors in these regions play an important role in the LH-mediated modulation of nociceptive information in the acute model of pain in the rats. It seems that this pain modulating system is more relevant to D2-like receptors in the nucleus accumbens.

Evidence from animal models suggests a role for orexinergic system in reward processing and drug addiction. The lateral hypothalamus (LH) orexin neurons send projections to the dorsal hippocampus (CA1 region) which plays a pivotal role in reward processes. Moreover, it has been shown that orexin containing terminals and orexin receptors are distributed in the hippocampal formation. In this study, we assessed the role of orexin 1 (OX1r) and orexin2 (OX2r) receptors in the CA1 on the development of LH stimulation-induced conditioned place preference (CPP). Animals weighing 230-280 g were unilaterally implanted by two separate cannulae into the LH and CA1. The CPP paradigm was done; SB334867 and TCSOX229, as selective OX1r and OX2r antagonists (1, 3, 10 and 30 nM/0.5 μl DMSO) administrated into the CA1 prior to intra-LH carbachol microinjection (250 nM; the most effective dose) during the 3-days conditioning phase, respectively. Conditioning scores and locomotor activities were recorded by Ethovision software on the test day. The results showed that the administration of OX1r and OX2r antagonists into the CA1 attenuated the development of CPP induced by chemical stimulation of the LH. However, this decrease in OX1r antagonist treated groups was more significant than that in OX2r antagonist treated animals. Our findings suggest that OX1 and OX2 receptors in the CA1 region of the hippocampus were involved in the development of CPP induced by chemical stimulation of the LH and the efficiency of OX1 receptors in this phenomenon was more considerable than OX2 receptors in rats.