Huang Dan, Zhang Lu, Yang Jun-Qing, Luo Ying, Cui Ting, Du Ting-Ting, Jiang Xin-Hui
School of Pharmacy, Chongqing Medical University, Chongqing, 400016, China.
West China-Washington Mitochondria and Metabolism Center, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China.
Genes Dis. 2018 Jun 15;6(2):167-175. doi: 10.1016/j.gendis.2018.05.005. eCollection 2019 Jun.
Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression. To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats, sertraline, and meloxicam, the inhibitors of arachidonic acid - cyclooxygenase-2/lipoxygenase (AA-COX-2/5-LO) pathways, were given to depressive rats. After the development of depression model by chronic unpredictable mild stress (CUMS) for 6 weeks, Successful modeling rats were selected and randomly divided into CUMS group and medication administration group. After given medicine, The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector (HPLC-ECD). Compared with the normal group, the concentration of norepinephrine (NE) significantly decreased and the concentrations of Tyrosine (Tyr), Tryptophan (Trp), 3,4-dihydroxyphenyl acetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) significantly increased in the CUMS group. Sertraline significantly inhibited the elevation of 5-HIAA. Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp, MHPG, and 5-HIAA level in a dose-dependent manner. Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner. The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMS-induced changes in biogenic amines. Compared with the single-dose lipoxygenase (5-LO) or Cyclooxygenase-2 (COX-2) inhibitor, the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.
炎症促使抑郁症的发展，可能影响神经递质，进而使神经回路增加患抑郁症的风险。为了研究抑制炎症途径对抑郁大鼠生物胺神经递质代谢的影响，将花生四烯酸 - 环氧化酶 - 2/脂氧合酶（AA - COX - 2/5 - LO）途径的抑制剂舍曲林和美洛昔康给予抑郁大鼠。通过慢性不可预测轻度应激（CUMS）建立抑郁模型6周后，选择造模成功的大鼠并随机分为CUMS组和给药组。给药后，采用配备电化学检测器的高效液相色谱法（HPLC - ECD）测定大鼠皮质和海马中的生物胺神经递质。与正常组相比，CUMS组去甲肾上腺素（NE）浓度显著降低，酪氨酸（Tyr）、色氨酸（Trp）、3,4 - 二羟基苯乙酸（DOPAC）、3 - 甲氧基 - 4 - 羟基苯乙二醇（MHPG）、高香草酸（HVA）和5 - 羟吲哚乙酸（5 - HIAA）浓度显著升高。舍曲林显著抑制5 - HIAA的升高。美洛昔康剂量依赖性地抑制CUMS诱导大鼠NE水平的降低以及Trp、MHPG和5 - HIAA水平的升高。咖啡酸剂量依赖性地抑制NE的降低以及Trp和MHPG的升高。抑制AA - COX - 2/5 - LO途径可改善抑郁大鼠的行为，并抑制CUMS诱导的生物胺变化。与单剂量脂氧合酶（5 - LO）或环氧化酶 - 2（COX - 2）抑制剂相比，美洛昔康1mg/kg与咖啡酸10mg/kg联合治疗对CUMS诱导的抑郁行为以及皮质单胺神经递质及其代谢产物水平没有显著改善。
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