Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.
Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.
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DOI：
10.1111/ejn.16064
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发表时间：
2023-06
影响因子：
3.4
通讯作者：
S. Valvassori;Taise Possamai-Della;Jorge M. Aguiar-Geraldo;Rômulo Goronci Sant'Ana;Gustavo C. Dal-Pont;Bruna B. Pescador;A. Zugno;J. Quevedo;F. Dal-Pizzol
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文献类型：
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作者：
S. Valvassori;Taise Possamai-Della;Jorge M. Aguiar-Geraldo;Rômulo Goronci Sant'Ana;Gustavo C. Dal-Pont;Bruna B. Pescador;A. Zugno;J. Quevedo;F. Dal-Pizzol
本研究旨在评价脓毒症是否会使间苯异丙胺诱导的行为和生化反应敏感。为此，对Wistar大鼠进行盲肠结扎和穿刺。盲肠结扎和穿刺手术30天后，对动物进行单次腹膜内注射生理盐水或间苯异丙胺（0.25、0.50或1.0 mg/kg）。给药后2小时评估运动行为。在额叶皮质、海马和纹状体中评价了白细胞介素（IL）-1 β、IL-6、IL-10、肿瘤坏死因子-α、多巴胺-cAMP调节的32，000 kDa磷蛋白（DARPP-32）和神经元钙传感器（NCS-1）水平。此外，还评估了海马中的脑源性神经营养因子（BDNF）、神经元生长因子和胶质源性神经营养因子水平。与Sham + Sal相比，单独的M-苯丙胺（0.25和1.0 mg/kg）增加了大鼠的运动和探索行为。与假手术+生理盐水组及其各自的假手术组相比，盲肠结扎和穿刺+间苯丙胺（0.5和/或1.0 mg/kg）组的动物显示出运动、探索和风险样行为增加。与Sham + Sal相比，盲肠结扎和穿孔增加了白细胞介素水平。然而，与Sham + Sal组和盲肠结扎和穿刺+生理盐水组相比，接受间苯丙胺（1 mg/kg）的盲肠结扎和穿刺动物的这些炎症参数增加更多。在盲肠结扎和穿刺大鼠的大脑中，较低剂量的甲基苯丙胺增加了神经营养因子，但较高剂量降低了这些参数。在盲肠结扎和穿孔大鼠的某些结构中，M-苯丙胺剂量依赖性地增加DARPP-32和NCS-1水平。总之，这些结果表明，脓毒症致敏行为安非他明反应，同时诱导盲肠结扎和穿刺模型中的炎症和神经营养脆弱性。
The present study aimed to evaluate if sepsis sensitizes behavioural and biochemical responses induced by m‐amphetamine. For this, Wistar rats were submitted to the cecal ligation and puncture. After 30 days of cecal ligation and puncture procedure, the animals were submitted to a single intraperitoneal injection of saline or m‐amphetamine (.25, .50, or 1.0 mg/kg). Locomotor behaviour was assessed 2 h after the administration. Interleukin (IL)‐1β, IL‐6, IL‐10, tumour necrosis factor‐α, dopamine‐cAMP‐regulated phosphoprotein of 32,000 kDa (DARPP‐32) and neuronal calcium sensor (NCS‐1) levels were evaluated in the frontal cortex, hippocampus and striatum. Also, brain‐derived neurotrophic factor (BDNF), neuronal growth factor and glial‐derived neurotrophic factor levels were assessed in the hippocampus. M‐amphetamine alone (.25 and 1.0 mg/kg) increased rats' locomotion and exploratory behaviour compared with the Sham + Sal. Animals from the cecal ligation and puncture + m‐amphetamine (.5 and/or 1.0 mg/kg) group showed an increase in locomotion, exploratory and risk‐like behaviour when compared with the Sham + Saline group and with its respective Sham groups. Cecal ligation and puncture increased interleukin levels compared with the Sham + Sal. However, cecal ligation and puncture animals that received m‐amphetamine (1 mg/kg) increased even more, these inflammatory parameters compared with the Sham + Sal and the cecal ligation and puncture + saline group. M‐amphetamine at lower doses increased neurotrophic factors, but higher doses decreased these parameters in the brain of cecal ligation and puncture rats. M‐amphetamine dose‐dependently increased DARPP‐32 and NCS‐1 levels in cecal ligation and puncture rats in some structures. In conclusion, these results demonstrate that sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model.