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首页> 外文期刊>The European Journal of Neuroscience >Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration.
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Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration.

机译:可卡因自我给药后灵长类纹状体中前强啡肽mRNA的时间上调。

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Several human and rat studies suggest that the striatal dynorphin system is important for neuroadaptation following cocaine exposure. In the current study, prodynorphin (PDYN) mRNA expression was examined in monkeys at initial and chronic phases of cocaine self-administration. Adult Rhesus monkeys were trained to self-administer food (banana flavoured pellets) or cocaine (0.03 or 0.3 mg/kg per injection) on a fixed interval 3-min schedule for 5 or 100 sessions. Each session ended after 30 reinforcers were delivered. The PDYN mRNA expression was analysed in the precommissural striatum using in situ hybridization histochemistry. We found a specific activation of PDYN mRNA expression in the limbic-innervated patch/striosome compartment of the dorsal caudate and dorsal putamen during the initial (i.e. 5 day) phase of the high dose cocaine self-administration. After 100 days of the high dose exposure, the patch/striosome compartment remained activated, but an increase in PDYN mRNA levels was also evident inthe sensorimotor-connected matrix compartment of the caudate. Neither self-administration phase resulted in significant changes in the corresponding striatal regions of the low dose cocaine-exposed primates. Moreover, cocaine self-administration failed to alter the PDYN mRNA expression in high- or low-expressing PDYN cell populations in the nucleus accumbens during any condition studied. These results demonstrate the vulnerability of the dorsal striatum (in particular the caudate) to neuroadaptations following long-term high dose cocaine self-administration. In addition, the temporal nature of the changes in PDYN gene expression within the striatal compartments could reflect a change in drug responsivity that occurs during the transition to drug dependence.
机译:多项人类和大鼠研究表明,可卡因暴露后,纹状体强啡肽系统对于神经适应很重要。在当前的研究中,在可卡因自我给药的初始阶段和慢性阶段,在猴子中检查了强啡肽(PDYN)mRNA的表达。训练成年恒河猴以固定间隔3分钟的时间表自我管理食物(香蕉味药丸)或可卡因(每次注射0.03或0.3 mg / kg),持续5或100次。每次会议都在派出30名援军后结束。使用原位杂交组织化学技术分析了合前前纹状体中PDYN mRNA的表达。我们发现在高剂量可卡因自我给药的初始阶段(即5天),在尾状背侧和背壳状核的边缘神经支配的膜/纹状体区室中,PDYN mRNA表达被特异性激活。在高剂量暴露100天后,贴片/质体间隔区保持激活状态,但尾状核的感觉运动相关基质区室中PDYN mRNA水平也明显升高。这两个自我给药阶段均未导致低剂量可卡因接触灵长类动物的相应纹状体区域发生明显变化。此外,在任何研究的条件下,可卡因自我给药均无法改变伏伏核中高表达或低表达PDYN细胞群体中PDYN mRNA的表达。这些结果表明,长期服用高剂量可卡因后,背侧纹状体(尤其是尾状)易受神经适应。另外,纹状体区室中PDYN基因表达变化的时间性质可能反映了在向药物依赖性过渡期间发生的药物反应性变化。

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