Phasic-like stimulation of the medial forebrain bundle augments striatal gene expression despite methamphetamine-induced partial dopamine denervation.
Phasic-like stimulation of the medial forebrain bundle augments striatal gene expression despite methamphetamine-induced partial dopamine denervation.
复制标题
尽管甲基苯丙胺诱导部分多巴胺去神经，但内侧前脑束的阶段性刺激增强了纹状体基因表达。
DOI：
10.1111/jnc.12234
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发表时间：
2013
影响因子：
4.7
通讯作者：
Keefe,KristenA
中科院分区：
文献类型：
--
作者：
Howard,ChristopherD;Pastuzyn,ElissaD;Barker-Haliski,MelissaL;Garris,PaulA;Keefe,KristenA
甲基苯丙胺诱导的部分多巴胺消耗与基底神经节功能受损有关，包括纹状体中proprotachykininmrna表达减少和活性调节的细胞骨架相关（Arc）基因的转录激活受损。最近的研究表明，相多巴胺信号缺陷可能是甲基苯丙胺诱导的多巴胺丢失与基底神经节功能受损相关的潜在机制。因此，本研究试图通过确定纹状体神经元基因表达的缺陷是否可以通过增加阶段性多巴胺释放来恢复，从而建立相多巴胺传递与基底神经节功能改变之间的因果关系。在生理盐水预处理或甲基苯丙胺神经毒性治疗方案三周后，大鼠接受了对上行多巴胺神经元的相位或强直性刺激。采用原位杂交组织化学检测纹状体基因表达。尽管在甲基苯丙胺预处理的大鼠中出现了部分纹状体多巴胺去神经支配，但在两组中，相样而非强直样刺激均诱导了即时早期基因arcandzif268， arch表达发生在假定的纹状体输出神经元中。相样刺激也恢复了proprotachykininmrna的表达。这些结果表明，阶段性多巴胺信号的破坏可能是甲基苯丙胺诱导的基底神经节功能损伤的基础，恢复阶段性多巴胺信号可能是一种可行的方法，可以管理甲基苯丙胺诱导的基底神经节功能多巴胺损失的长期后果。
Methamphetamine‐induced partial dopamine depletions are associated with impaired basal ganglia function, including decreasedpreprotachykininmRNA expression and impaired transcriptional activation of activity‐regulated, cytoskeleton‐associated (Arc) gene in striatum. Recent work implicates deficits in phasic dopamine signaling as a potential mechanism linking methamphetamine‐induced dopamine loss to impaired basal ganglia function. This study thus sought to establish a causal link between phasic dopamine transmission and altered basal ganglia function by determining whether the deficits in striatal neuron gene expression could be restored by increasing phasic dopamine release. Three weeks after pretreatment with saline or a neurotoxic regimen of methamphetamine, rats underwent phasic‐ or tonic‐like stimulation of ascending dopamine neurons. Striatal gene expression was examined usingin situhybridization histochemistry. Phasic‐like, but not tonic‐like, stimulation induced immediate‐early genesArcandzif268in both groups, despite the partial striatal dopamine denervation in methamphetamine‐pretreated rats, with theArcexpression occurring in presumed striatonigral efferent neurons. Phasic‐like stimulation also restoredpreprotachykininmRNA expression. These results suggest that disruption of phasic dopamine signaling likely underlies methamphetamine‐induced impairments in basal ganglia function, and that restoring phasic dopamine signaling may be a viable approach to manage long‐term consequences of methamphetamine‐induced dopamine loss on basal ganglia functions.