Basolateral Amygdala Serotonin 2C Receptor Regulates Emotional Disorder-Related Symptoms Induced by Chronic Methamphetamine Administration.
Basolateral Amygdala Serotonin 2C Receptor Regulates Emotional Disorder-Related Symptoms Induced by Chronic Methamphetamine Administration.
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DOI：
10.3389/fphar.2021.627307
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发表时间：
2021
影响因子：
5.6
通讯作者：
Qiu P
中科院分区：
文献类型：
--
作者：
Wang Z;Li C;Ding J;Li Y;Zhou Z;Huang Y;Wang X;Fan H;Huang J;He Y;Li J;Chen J;Qiu P
在全球范围内，甲基苯丙胺是第二大滥用药物，精神病症状是最常见的不良反应之一。MA滥用引起的情绪障碍已被广泛报道在人类和动物模型，然而，这种疾病的机制尚未完全阐明。在这项研究中，慢性MA给药小鼠模型被用来阐明参与MA诱导的情绪障碍的多巴胺能通路。MA给药4周后，动物表现出显著增加的抑郁和焦虑症状。分子和形态学证据表明，长期MA管理减少5-羟色胺（5-HT）限速酶，色氨酸羟化酶2，中缝背核和5-HT及其代谢产物5-羟吲哚乙酸的浓度在基底外侧杏仁核（BLA）的表达。5-HT和5-HT受体水平的改变同时发生在BLA;定量聚合酶链反应，免疫印迹和荧光分析显示，5-HT 2C受体（5-HT 2CR）的表达增加。神经药理学和病毒介导的沉默策略证实，靶向5-HT 2CR逆转慢性MA给药诱导的抑郁和焦虑行为。在BLA中，5-HT 2CR阳性细胞与GABA能中间神经元共定位。5-HT 2CR的失活可改善受损的GABA能抑制和降低BLA激活。因此，在此，我们首次报道了5-HT 2CR的异常调节参与慢性MA使用引起的情绪障碍样症状的表现。我们的研究表明，5-HT 2CR在BLA是一个有前途的临床目标，用于治疗MA诱导的情绪障碍。
Globally, methamphetamine (MA) is the second most abused drug, with psychotic symptoms being one of the most common adverse effects. Emotional disorders induced by MA abuse have been widely reported both in human and animal models; however, the mechanisms underlying such disorders have not yet been fully elucidated. In this study, a chronic MA administration mouse model was utilized to elucidate the serotonergic pathway involved in MA-induced emotional disorders. After 4 weeks of MA administration, the animals exhibited significantly increased depressive and anxious symptoms. Molecular and morphological evidence showed that chronic MA administration reduced the expression of the 5-hydroxytryptamine (5-HT) rate-limiting enzyme, tryptophan hydroxylase 2, in the dorsal raphe and the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid in the basolateral amygdala (BLA) nuclei. Alterations in both 5-HT and 5-HT receptor levels occurred simultaneously in BLA; quantitative polymerase chain reaction, western blotting, and fluorescence analysis revealed that the expression of the 5-HT2C receptor (5-HT2CR) increased. Neuropharmacology and virus-mediated silencing strategies confirmed that targeting 5-HT2CR reversed the depressive and anxious behaviors induced by chronic MA administration. In the BLA, 5-HT2CR-positive cells co-localized with GABAergic interneurons. The inactivation of 5-HT2CR ameliorated impaired GABAergic inhibition and decreased BLA activation. Thus, herein, for the first time, we report that the abnormal regulation of 5-HT2CR is involved in the manifestation of emotional disorder-like symptoms induced by chronic MA use. Our study suggests that 5-HT2CR in the BLA is a promising clinical target for the treatment of MA-induced emotional disorders.
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影响因子：
4.4
作者：
Casaletto, K. B.;Obermeit, L.;Morgan, E. E.;Weber, E.;Franklin, D. R.;Grant, I.;Woods, S. P.
通讯作者：
Woods, S. P.
影响因子：
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作者：
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作者：
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影响因子：
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作者：
Cao, Xiong;Li, Liang-Ping;Gao, Tian-Ming
通讯作者：
Gao, Tian-Ming