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首页> 外文期刊>The European Journal of Neuroscience >Topography of cocaine-induced gene regulation in the rat striatum: relationship to cortical inputs and role of behavioural context.
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Topography of cocaine-induced gene regulation in the rat striatum: relationship to cortical inputs and role of behavioural context.

机译：可卡因诱导的大鼠纹状体基因调控的地形：与皮层输入的关系和行为背景的作用。

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Psychostimulants alter gene expression in projection neurons of the striatum, and such neuroplasticity is implicated in drug addiction and dependence. Evidence indicates that excitatory inputs from the cortex and thalamus are critical for these molecular changes. In the present study, we determined the topography of cocaine-induced changes in gene expression in the rat striatum and investigated whether these molecular alterations are associated with particular cortical inputs. Acute induction of c-fos (by 25 mg/kg of cocaine), and the c-fos response and dynorphin expression after repeated cocaine treatment (25 mg/kg, 4 days) were assessed as examples for short-term and longer-term molecular changes, respectively. In addition, we examined whether these molecular effects were influenced by the behaviour performed during cocaine action (running-wheel training vs. open field). Our results demonstrate that the overall topography of cocaine-induced gene regulation in the striatum is remarkably stable. Both acute and longer-term molecular changes were maximal in caudal dorsal striatal sectors that receive convergent inputs from the medial agranular and the sensorimotor cortex. In contrast, relatively minor or no effects were found in rostral and ventral striatal sectors. However, running-wheel training under the influence of cocaine enhanced the c-fos response to a subsequent cocaine challenge selectively in parts of the caudal sensorimotor striatum. These results indicate that cocaine produces molecular adaptations preferentially in cortico-basal ganglia circuits through the sensorimotor striatum, and that some of these neuronal changes are influenced by the behaviour performed during drug exposure.
机译：精神兴奋剂改变纹状体投射神经元中的基因表达，并且这种神经可塑性与药物成瘾和依赖性有关。有证据表明，皮层和丘脑的兴奋性输入对于这些分子变化至关重要。在本研究中，我们确定了可卡因诱导的大鼠纹状体基因表达变化的地形，并研究了这些分子变化是否与特定的皮质输入有关。以短期和长期为例，评估了急性诱导c-fos（25 mg / kg可卡因）以及反复可卡因治疗（25 mg / kg，4天）后c-fos反应和强啡肽的表达。分子变化。此外，我们检查了这些分子效应是否受到可卡因动作期间行为的影响（飞轮训练与空地训练）。我们的结果表明，可卡因诱导的纹状体基因调控的总体拓扑结构非常稳定。急性和长期分子变化在接受来自内侧颗粒和感觉运动皮层的会聚输入的尾背纹状体区域中最大。相反，在鼻和腹侧纹状体中没有发现相对较小的影响。然而，在可卡因的影响下进行的转轮训练在尾部感觉运动纹状体的某些部位选择性地增强了对随后可卡因攻击的c-fos反应。这些结果表明可卡因通过感觉运动纹状体优先在皮质基底神经节回路中产生分子适应性，并且这些神经元变化中的一些受到药物暴露过程中行为的影响。

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