Activation and blockade of basolateral amygdala 5-HT6 receptor produce anxiolytic-like behaviors in an experimental model of Parkinson's disease.
Activation and blockade of basolateral amygdala 5-HT6 receptor produce anxiolytic-like behaviors in an experimental model of Parkinson's disease.
复制标题
在帕金森病的实验模型中，基底外侧杏仁核 5-HT6 受体的激活和阻断会产生抗焦虑样行为。
DOI：
10.1016/j.neuropharm.2018.05.016
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发表时间：
2018
影响因子：
4.7
通讯作者：
Jian Liu
中科院分区：
文献类型：
--
作者：
Yi-Na Sun;Lu Yao;Li-Bo Li;Yong Wang;Cheng-Xue Du;Yuan Guo;Jian Liu
虽然基底外侧杏仁核（BLA）和5-HT 6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 6受体参与焦虑在单侧6-羟基多巴胺诱导的PD大鼠。损毁内侧前脑束（MFB）可引起大鼠焦虑样行为，并使内侧前额叶皮质（mPFC）、杏仁核和海马腹侧部（vHip）的BLA谷氨酸神经元基础放电频率和多巴胺（DA）水平降低。局部注射WAY 208466激活BLA 5-HT 6受体，可诱导BLA的抗焦虑作用，并增加BLA细胞外γ-氨基丁酸（GABA）水平。SB 258585阻断BLA 5-HT 6受体产生抗焦虑样作用，并增加两组大鼠BLA中细胞外GABA水平。激活和阻断BLA 5-HT 6受体均导致两组大鼠mPFC、杏仁核和vHip组织中DA水平升高和去甲肾上腺素水平降低，并对假手术和损毁大鼠的谷氨酸神经元放电活动产生相反影响。结果提示，边缘脑区DA水平降低和BLA神经元5-HT_6受体敏感性增强可能是PD患者焦虑的病因和病理生理因素。WAY 208466和SB 258585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。
Although the basolateral amygdala (BLA) and serotonin6 (5-HT6) 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-HT6 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-HT6 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-HT6 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-HT6 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-HT6 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.