Gegen-Qinlian decoction—A traditional Chinese medicine formula—Alleviates methamphetamine withdrawal induced anxiety by targeting GABAergic interneuron-pyramidal neuron pathway in mPFC,Addiction Biology

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Gegen-Qinlian decoction—A traditional Chinese medicine formula—Alleviates methamphetamine withdrawal induced anxiety by targeting GABAergic interneuron-pyramidal neuron pathway in mPFC
Addiction Biology ( IF 3.1 ) Pub Date : 2023-07-30 , DOI: 10.1111/adb.13314
Hongxiu Song ₁ , Xue Lu ₁ , Demin Du ₁ , Yaqin Peng ₁ , Weichao Pan ₁ , Xing Xu ₁ , Yu Fan ₁ , Xin Yang ₁ , Feifei Ge ₁ , Xiaowei Guan ₁

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Methamphetamine (Meth) withdrawal elicits anxiety, which is a public health concern with limited therapeutic options. Previous studies implied a strong correlation between mPFC and Meth withdrawal. Here, we examined the role of Gegen-Qinlian decoction (GQD) in Meth withdrawal anxiety and explored potential therapeutic targets in mPFC. We found that intra-gastric administration of GQD during the withdrawal period efficiently alleviated anxiety-like behaviours in Meth-withdrawn mice. Further, GQD could restore Meth withdrawal-triggered pathway of GABAergic interneurons (GABA IN)-pyramidal neurons (PN) in the mPFC of Meth-withdrawn mice, especially the prelimbic cortex (PrL) sub-region and PV-positive GABA IN. While, GQD had no obvious effects on the glial cells in the mPFC of Meth-withdrawn mice. By transcriptomic analysis and validation of several gene candidates, we found that genes in the MAPK signalling pathway, especially those related to heat shock proteins, including Hspa1a, Hspa1b and Hspb1, might be GQD-targeting genes in mPFC to treat Meth withdrawal anxiety, as indicated that these genes were up-regulated by Meth withdrawal but rescued by GQD in mPFC. Collectively, our findings identified for the first time that GQD could efficiently alleviate Meth withdrawal anxiety, partially through regulating the local GABA IN-PN pathway and transcriptomic profile of mPFC. The present study confirms that TCM, such as GQD, will be a desirable therapeutic approach in the treatment of drug addiction and related emotional deficits.

中文翻译：

葛根芩连汤——中药方——通过靶向mPFC中GABA能中间神经元-锥体神经元通路缓解甲基苯丙胺戒断引起的焦虑

甲基苯丙胺（Meth）戒断会引起焦虑，这是一个公共健康问题，治疗选择有限。先前的研究表明 mPFC 与冰毒戒断之间存在很强的相关性。在这里，我们研究了葛根芩连汤（GQD）在冰毒戒断焦虑中的作用，并探索了 mPFC 的潜在治疗靶点。我们发现，在戒断期间胃内给予 GQD 可以有效缓解戒断小鼠的焦虑样行为。此外，GQD 可以恢复 Meth 戒断小鼠 mPFC 中 GABA 能中间神经元 (GABA IN)-锥体神经元 (PN) 的 Meth 戒断触发通路，特别是前边缘皮层 (PrL) 亚区和 PV 阳性 GABA IN。而GQD对停药小鼠mPFC中的胶质细胞没有明显影响。通过对几个候选基因的转录组分析和验证，我们发现 MAPK 信号通路中的基因，特别是与热休克蛋白相关的基因，包括Hspa1a、Hspa1b和Hspb1，可能是 mPFC 中治疗冰毒戒断焦虑的 GQD 靶向基因，如表明这些基因在 mPFC 中因冰毒戒断而上调，但被 GQD 拯救。总的来说，我们的研究结果首次确定 GQD 可以有效缓解冰毒戒断焦虑，部分是通过调节局部 GABA IN-PN 通路和 mPFC 的转录组图谱。目前的研究证实，中医（如 GQD）将成为治疗毒瘾和相关情绪缺陷的理想治疗方法。

更新日期：2023-08-02

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