丙戊酸镁对甲基苯丙胺成瘾大鼠的作用及机制

IF 2.6 3区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuanrong Li, Lixin Wang, Youhui Sun, Xuyi Wang
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引用次数: 0

摘要

丙戊酸盐有望成为一种治疗成瘾的药物。然而,关于丙戊酸镁(VPA-Mg)对甲基苯丙胺(MA)成瘾作用的研究有限,相关机制尚未得到深入讨论。本研究旨在探讨VPA-Mg对MA成瘾的潜在治疗作用,并探讨其可能机制。采用条件位置偏好(CPP)和行为致敏模型研究了VPA-Mg对大鼠MA成瘾的影响。在CPP形成和消失阶段给予VPA-Mg,以评估其对ma诱导的CPP形成和恢复的影响。行为致敏评估了VPA-Mg在致敏诱导和表达阶段的影响,事先优化了自发活性和MA剂量。采用western blotting对大鼠前额皮质(PFC)、海马(Hip)、伏隔核(NAc)和腹侧被盖区(VTA)等脑区进行western blotting检测糖原合成酶激酶3β (GSK-3β)和多巴胺转运体(DAT)蛋白水平。VPA-Mg对ma诱导的CPP形成无显著影响。VPA-Mg显著降低ma诱导的行为致敏的建立和表达(p < 0.01)。表达期前3天用VPA-Mg预处理也能抑制致敏(p < 0.05)。此外,行为致敏大鼠PFC、Hip和VTA中p- gsk -3β与t-GSK-3β的比值显著降低,DAT表达显著降低(p < 0.01)。VPA-Mg可以逆转反复使用MA引起的髋部GSK-3β活性升高、PFC和髋部DAT降低(p < 0.05)。VPA-Mg具有抗MA依赖和预防复发的作用。成瘾相关脑区(PFC, Hip, VTA)的GSK-3β激活和DAT下调与MA成瘾密切相关,提示潜在的治疗靶点。VPA-Mg可能通过调节这些通路发挥作用,特别是在PFC和Hip中。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

The Effect and Mechanism of Magnesium Valproate on Methamphetamine-Addicted Rats

The Effect and Mechanism of Magnesium Valproate on Methamphetamine-Addicted Rats

Valproate may hold promise as a treatment for addiction. However, there are limited studies examining the effects of magnesium valproate (VPA-Mg) on methamphetamine (MA) addiction, and the relevant mechanisms have not been thoroughly discussed. This study aims to explore the potential therapeutic effects of VPA-Mg on MA addiction and to investigate its possible mechanisms. The effects of VPA-Mg on MA addiction were investigated using conditioned place preference (CPP) and behavioural sensitisation models in rats. VPA-Mg was administered during CPP formation and extinction phases to evaluate its effects on MA-induced CPP formation and reinstatement. Behavioural sensitisation assessed the impact of VPA-Mg during sensitisation induction and expression phases, with spontaneous activity and MA dosing optimised beforehand. Furthermore, western blotting was performed on brain regions including the prefrontal cortex (PFC), hippocampus (Hip), nucleus accumbens (NAc) and ventral tegmental area (VTA) to measure glycogen synthase kinase 3 beta (GSK-3β) and dopamine transporter (DAT) protein levels. VPA-Mg did not exhibit a significant impact on MA-induced CPP formation. VPA-Mg significantly reduced the establishment and expression of MA-induced behavioural sensitisation (p < 0.01). Pre-treatment with VPA-Mg for 3 days before the expression period also inhibited sensitisation (p < 0.05). In addition, the ratio of p-GSK-3β to t-GSK-3β in the PFC, Hip and VTA of rats with behavioural sensitisation significantly decreased, and the expression of DAT decreased significantly (p < 0.01). VPA-Mg can reverse the increase in GSK-3β activity in the Hip and the decrease in DAT in the PFC and Hip caused by repeated MA use (p < 0.05). VPA-Mg exhibits anti-addictive effects on MA dependence and relapse prevention. GSK-3β activation and DAT downregulation in addiction-related brain regions (PFC, Hip, VTA) are closely linked to MA addiction, suggesting potential therapeutic targets. VPA-Mg may exert its effects by modulating these pathways, particularly in the PFC and Hip.

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来源期刊
Addiction Biology
Addiction Biology 生物-生化与分子生物学
CiteScore
8.10
自引率
2.90%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.
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