Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration
Temporal upregulation of prodynorphin mRNA in the primate striatum after cocaine self-administration
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DOI：
10.1046/j.1460-9568.2003.02636.x
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发表时间：
2003-05-01
影响因子：
3.4
通讯作者：
Hurd, YL
中科院分区：
文献类型：
--
作者：
Fagergren, P;Smith, HR;Hurd, YL
一些人和大鼠的研究表明，纹状体强啡肽系统对于可卡因暴露后的神经适应非常重要。在目前的研究中，检测了可卡因给药初期和慢性阶段猴子的前强啡肽(PDYN)mRNA的表达。成年恒河猴被训练成自我给药(香蕉味颗粒)或可卡因(每次注射0.03或0.3 mg/kg)，固定间隔3分钟，共5次或100次。每一次会议在30个增强剂交付后结束。用原位杂交组织化学方法检测连合前纹状体内PDYN基因的表达。我们发现在大剂量可卡因给药的初期(即5天)，PDYN基因在尾状背核和背壳核边缘神经支配的斑块/纹状体亚室有特异性的激活。在100天的高剂量照射后，斑块/纹状体小体间隔仍然处于激活状态，但在尾状核的感觉运动连接的基质间隔中，PDYN mRNA水平也明显增加。两个给药阶段均未引起低剂量可卡因暴露的灵长类动物相应纹状体区域的显著变化。此外，在所研究的任何条件下，可卡因自身给药都不能改变伏隔核高表达或表达LOVE的PDYN细胞群中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(尤其是尾状核)对神经适应的脆弱性。此外，纹状体间隔内PDYN基因表达变化的时间性质可能反映了在药物依赖过渡期间发生的药物反应性的变化。
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 in the 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 love-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.