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海马多巴胺受体在急性疼痛动物模型中,侧下丘脑化学刺激引起的抗伤害反应中的作用。

Role of hippocampal dopamine receptors in the antinociceptive responses induced by chemical stimulation of the lateral hypothalamus in animal model of acute pain.

机构信息

Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Brain Res. 2020 May 1;1734:146759. doi: 10.1016/j.brainres.2020.146759. Epub 2020 Mar 2.

Abstract

Dopamine is the predominant catecholamine neurotransmitter in the mammalian brain which has been shown to play a critical role in antinociceptive process. Previous studies have shown that the role of CA1 region of the hippocampus in antinociception induced by stimulation of the lateral hypothalamus (LH) through the dopaminergic system in tonic pain. In this study, we tried to assess the involvement of intra-hippocampal D1- and D2-like dopamine receptors in the LH stimulation-induced antinociception during the tail-flick test as an animal model of acute pain. Ninety-five male Wistar rats were unilaterally implanted with two separate cannulae into the LH and CA1. Animals received intra-CA1 infusion of SCH-23390 (0.25, 1 and 4 µg/rat), as a D1-like dopamine receptor antagonist and sulpiride (0.125, 0.25, 1 and 4 µg/rat), as a D2-like dopamine receptor antagonist, 2 min before intra-LH administration of carbachol (250 nM/rat). The antinociceptive effects of SCH-23390 and sulpiride were measured by using a tail-flick analgesiometer and represented as the maximal possible effect (%MPE). Also, the locomotion tracking apparatus was used to measure the locomotor activity of animals. Results showed that intra-CA1 administration of SCH-23390 or sulpiride could prevent the intra-LH carbachol-induced antinociception. This effect was a little more dominant after blocking the D2-like dopamine receptor in the CA1. These findings revealed that D1- and D2-like dopamine receptors within the CA1 play an important role in antinociceptive responses induced by chemical stimulation of the LH. It could be suggested that dopamine receptors in the CA1 were triggered by LH orexinergic projections.

摘要

多巴胺是哺乳动物大脑中主要的儿茶酚胺神经递质,已被证明在抗伤害感受过程中发挥关键作用。先前的研究表明,海马 CA1 区在通过多巴胺能系统在慢性疼痛中刺激外侧下丘脑 (LH) 诱导的抗伤害感受中的作用。在这项研究中,我们试图评估海马内 D1-和 D2-样多巴胺受体在 LH 刺激诱导的尾部闪烁测试中的参与,作为急性疼痛的动物模型。95 只雄性 Wistar 大鼠单侧海马内植入两个单独的套管。动物在 CA1 内接受 SCH-23390(0.25、1 和 4 µg/大鼠),作为 D1-样多巴胺受体拮抗剂和舒必利(0.125、0.25、1 和 4 µg/大鼠),作为 D2-样多巴胺受体拮抗剂,在 CA1 内给予 carbachol(250 nM/大鼠)之前 2 分钟。用尾部闪烁镇痛仪测量 SCH-23390 和舒必利的抗伤害作用,并表示为最大可能效应(%MPE)。还使用运动跟踪装置测量动物的运动活动。结果表明,CA1 内给予 SCH-23390 或舒必利可预防 CA1 内 carbachol 诱导的抗伤害感受。在 CA1 内阻断 D2-样多巴胺受体后,这种作用更为明显。这些发现表明,CA1 内的 D1-和 D2-样多巴胺受体在 LH 化学刺激诱导的抗伤害反应中发挥重要作用。可以认为,CA1 中的多巴胺受体被 LH 食欲素投射触发。

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