Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
Department of Rehabilitation Medicine, The Second Hospital, Xi'an Jiaotong University, Xi'an 710004, China.
Behav Brain Res. 2023 Jul 9;449:114488. doi: 10.1016/j.bbr.2023.114488. Epub 2023 May 9.
Parkinson's disease (PD) is commonly accompanied with anxiety, multiple studies indicate that the basolateral amygdaloid nucleus (BLA) is closely related to modulation of anxiety and expresses serotonin (5-HT) receptors, however, effects of BLA 5-HT receptors on anxiety-like behaviors are unclear, particularly in PD-related anxiety.
The open-field and elevated plus maze tests were used to examine anxiety-like behaviors. In vivo electrophysiology and microdialysis were performed to observe the firing activity of BLA neurons and GABA, glutamate, dopamine (DA) and 5-HT release in the BLA, respectively. Western blotting was used to analyze protein expression of 5-HT receptors, adenylate cyclase (AC) and phosphorylated protein kinase A at threonine 197 site (p-PKA-Thr197) in the BLA.
Intra-BLA injection of 5-HT receptor agonist CP93129 produced anxiety-like effects and antagonist SB216641 induced anxiolytic-like responses in sham-operated and 6-hydroxydopamine-lesioned rats. Further, pretreatment with AC inhibitor SQ22536 and PKA inhibitor KT5720 blocked the behavioral effects of CP93129, respectively. Intra-BLA injection of CP93129 increased the firing rate of BLA glutamate neurons and decreased GABA/glutamate ratio and DA and 5-HT levels in the BLA of sham-operated and the lesioned rats, while SB216641 induced the opposite effects. Compared with sham-operated rats, effects of CP93129 and SB216641 on behaviors, electrophysiology and microdialysis were decreased in the lesioned rats, which were associated with decreased expression of 5-HT receptors, AC and p-PKA-Thr197 in the BLA.
These findings suggest that 5-HT receptor-AC-PKA signal pathway in the BLA is involved in the regulation of PD-related anxiety.
帕金森病（PD）常伴有焦虑，多项研究表明，基底外侧杏仁核（BLA）与调节焦虑密切相关，并表达 5-羟色胺（5-HT）受体，但 BLA 5-HT 受体对焦虑样行为的影响尚不清楚，特别是在 PD 相关焦虑中。
采用旷场实验和高架十字迷宫实验检测焦虑样行为。通过在体电生理学和微透析技术观察 BLA 神经元的放电活动以及 BLA 中 GABA、谷氨酸、多巴胺（DA）和 5-HT 的释放。Western blot 分析 BLA 中 5-HT 受体、腺苷酸环化酶（AC）和磷酸化蛋白激酶 A 第 197 位丝氨酸（p-PKA-Thr197）的蛋白表达。
BLA 内注射 5-HT 受体激动剂 CP93129 可产生焦虑样效应，而拮抗剂 SB216641 可在假手术和 6-羟多巴胺损伤大鼠中诱导抗焦虑样反应。此外，AC 抑制剂 SQ22536 和 PKA 抑制剂 KT5720 分别阻断 CP93129 的行为效应。BLA 内注射 CP93129 增加了 sham 手术和损伤大鼠 BLA 谷氨酸神经元的放电率，并降低了 BLA 中 GABA/谷氨酸比值和 DA 和 5-HT 水平，而 SB216641 则产生相反的效果。与 sham 手术大鼠相比，CP93129 和 SB216641 对行为、电生理和微透析的作用在损伤大鼠中降低，这与 BLA 中 5-HT 受体、AC 和 p-PKA-Thr197 的表达减少有关。
这些发现表明，BLA 中的 5-HT 受体-AC-PKA 信号通路参与了 PD 相关焦虑的调节。
