Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China.
Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education of China, Xi'an, 710061, China.
Neuropharmacology. 2018 Jul 15;137:275-285. doi: 10.1016/j.neuropharm.2018.05.016. Epub 2018 May 25.
Although the basolateral amygdala (BLA) and serotonin (5-HT) receptor are involved in modulation of anxiety, their roles in Parkinson' disease (PD)-related anxiety are still unknown. Thus we perform this study to examine the involvement of BLA 5-HT receptor on anxiety in unilateral 6-hydroxydopamine-induced PD rats. The lesion of the medial forebrain bundle (MFB) induced anxiety-like behaviors, and decreased the basal firing rate of BLA glutamate neurons and dopamine (DA) levels in tissues of the medial prefrontal cortex (mPFC), amygdala and ventral part of hippocampus (vHip) in rats. Activation of BLA 5-HT receptor by local infusion of WAY208466 induced anxiolytic-like effects and increased extracellular γ-aminobutyric acid (GABA) level in the BLA in the lesioned rats. Blockade of BLA 5-HT receptor by SB258585 produced anxiolytic-like effects and increased extracellular GABA levels in the BLA in two groups of rats. Activation and blockade of BLA 5-HT receptor resulted in increases in DA levels and decreases in noradrenaline levels in tissues of the mPFC, amygdala and vHip in two groups of rats, and induced opposite effects on the firing activity of glutamate neurons between sham-operated and the lesioned rats. The results suggest that decreased DA levels in the limbic brain regions and the enhanced sensitivity of the 5-HT receptor on the BLA neurons might be etiological and pathophysiological factors for anxiety in PD. The anxiolytic-like effects may due to elevated extracellular GABA levels in the BLA and altered monoamine levels in the limbic regions, which were induced by WAY208466 and SB258585 through different mechanisms.
尽管基底外侧杏仁核（BLA）和 5-羟色胺（5-HT）受体参与了焦虑的调节，但它们在帕金森病（PD）相关焦虑中的作用仍不清楚。因此，我们进行了这项研究，以检查 BLA 5-HT 受体在单侧 6-羟多巴胺诱导的 PD 大鼠焦虑中的作用。中脑导水管周围灰质（MFB）的损伤诱导出类似焦虑的行为，并降低了内侧前额叶皮质（mPFC）、杏仁核和海马腹侧部（vHip）组织中 BLA 谷氨酸神经元的基础放电率和多巴胺（DA）水平。通过局部输注 WAY208466 激活 BLA 5-HT 受体可产生抗焦虑样作用，并增加损伤大鼠 BLA 中的细胞外γ-氨基丁酸（GABA）水平。通过 SB258585 阻断 BLA 5-HT 受体可产生抗焦虑样作用，并增加两组大鼠 BLA 中的细胞外 GABA 水平。激活和阻断 BLA 5-HT 受体可增加 mPFC、杏仁核和 vHip 组织中的 DA 水平，降低去甲肾上腺素水平，并且在假手术和损伤大鼠的谷氨酸神经元放电活动中产生相反的作用。结果表明，边缘脑区 DA 水平降低和 BLA 神经元 5-HT 受体敏感性增强可能是 PD 焦虑的病因和病理生理因素。WAY208466 和 SB258585 通过不同的机制诱导 BLA 细胞外 GABA 水平升高和边缘区单胺水平改变，从而产生抗焦虑样作用。
