Cellular and Molecular Research Center and Department of Physiology, Qazvin University of Medical Sciences, Qazvin, Iran.
Pharmacol Biochem Behav. 2013 Apr;105:193-8. doi: 10.1016/j.pbb.2013.02.011. Epub 2013 Mar 5.
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 200-250g 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 250nmol/0.5μl 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 10nmol/rat), just 5min 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 60min after their administrations. The results showed that unilateral intra-LH administration of carbachol (125 and 250nmol/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, 5min 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.
先前的研究表明，用卡巴胆碱对外侧下丘脑（LH）进行化学刺激在尾闪烁测试中作为急性疼痛模型具有重要的镇痛作用。在这项研究中，我们试图评估腹侧被盖区（VTA）和伏隔核（NAc）中的食欲素-1 受体在 LH 刺激引起的大鼠镇痛反应中的参与。将 120 只成年雄性白化 Wistar 大鼠（体重 200-250g）单侧植入两个单独的 LH 导管，以及 VTA 或 NAc。本研究评估了两种剂量的 LH 内注射卡巴胆碱（125 和 250nmol/0.5μl 生理盐水）的镇痛作用，作为一种胆碱能激动剂。在另一组实验中，动物在 VTA 或 NAc 内输注 SB334867 作为选择性食欲素-A 受体拮抗剂（0.3、1、3 和 10nmol/大鼠），在将有效剂量的卡巴胆碱注入 LH 前 5 分钟。在尾闪烁测试中，通过尾闪烁镇痛计获得药物的镇痛反应，并表示为给药后 5、15、30、45 和 60 分钟的最大可能效应（%MPE）。结果表明，单侧 LH 内注射卡巴胆碱（125 和 250nmol/大鼠）诱导大鼠镇痛（P<0.01）。这两个剂量的镇痛作用没有显著差异。在我们研究的第二部分中，在 LH 内注射卡巴胆碱前 5 分钟，VTA 和 NAc 内给予不同剂量的 SB334867，可剂量依赖性地预防 LH 刺激诱导的镇痛作用的发展。然而，在 NAc 中的效果较小。据推测，来自 LH 的食欲素投射到 VTA 和 NAc 直接/间接参与 LH 化学刺激引起的镇痛，并且腹侧被盖区中的食欲素-1 受体在这种现象中具有更重要的作用。
