HIV-1 Proteins Influence Novelty-Seeking Behavior and Alter Region-Specific Transcriptional Responses to Chronic Nicotine Treatment in HIV-1Tg Rats.
HIV-1 Proteins Influence Novelty-Seeking Behavior and Alter Region-Specific Transcriptional Responses to Chronic Nicotine Treatment in HIV-1Tg Rats.
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HIV-1 蛋白影响 HIV-1Tg 大鼠的猎奇行为并改变对慢性尼古丁治疗的区域特异性转录反应。
DOI：
10.1093/ntr/ntx047
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Li,MingD
中科院分区：
文献类型：
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作者：
Yang,Zhongli;Nesil,Tanseli;Wingo,Taylor;Chang,SulieL;Li,MingD
临床研究表明，hiv -1感染患者比一般人群更容易使用或滥用成瘾性药物。我们假设HIV-1蛋白影响新奇寻求行为，并增强与新奇寻求行为和药物成瘾有关的基因对尼古丁的转录反应。方法在野外实验中，通过比较HIV-1Tg与F344对照大鼠的基线活性差异，评估HIV-1蛋白对求新行为的影响。行为测试后第一天，所有大鼠开始每天皮下注射尼古丁（0.4 mg/kg，碱）或生理盐水（每只大鼠相同），持续27天。在治疗结束时，收集前额皮质、伏隔核和腹侧被盖区进行多巴胺、GABA、谷氨酸和血清素受体家族基因的RNA表达分析。结果在中心移动距离上存在显著的品系差异，HIV-1Tg大鼠比F344大鼠在中心移动距离更大。定量RT-PCR分析显示，与F344大鼠相比，HIV-1Tg大鼠前额皮质drd3和grm2以及腹侧被盖区drd5和gabra6 mRNA表达显著上调，而伏隔核drd5 mRNA表达下调。此外，与对照动物相比，在HIV-1Tg大鼠的每个大脑区域中，尼古丁显著调节了更多的成瘾相关基因。结论shiv -1蛋白可能影响药物成瘾和求新行为相关基因的表达，调控药物成瘾和求新行为相关基因的表达。shiv -1病毒蛋白和慢性尼古丁治疗影响HIV-1转基因大鼠大脑三个区域中涉及新奇寻求行为和成瘾的基因的表达。这些发现暗示HIV-1蛋白可能参与寻求新奇行为，并调节与药物成瘾和寻求新奇相关的基因表达。
IntroductionClinical studies suggest that HIV-1-infected patients are more likely to use or abuse addictive drugs than is the general population. We hypothesized that HIV-1 proteins impact novelty-seeking behavior and enhance the transcriptional response to nicotine in genes implicated in both novelty-seeking behavior and drug addiction.MethodsWe assessed the effects of HIV-1 proteins on novelty-seeking behavior by comparing baseline activity differences of HIV-1Tg and F344 control rats in the open-field test. One day after behavioral testing, all rats began daily subcutaneous injections of either nicotine (0.4 mg/kg, base) or saline (the same for each rat) for 27 days. At the end of treatment, the prefrontal cortex, nucleus accumbens, and ventral tegmental area were collected for RNA expression analysis of genes in the receptor families for dopamine, GABA, glutamate, and serotonin.ResultsSignificant strain difference was detected in the distance moved in the center, such that HIV-1Tg rats traveled greater distance in the center of the arena than did F344 rats. Quantitative RT-PCR analysis showed that mRNA fromDrd3andGrm2in the prefrontal cortex andDrd5andGabra6in the ventral tegmental area was significantly upregulated, whereas that ofDrd5in the nucleus accumbens was downregulated in HIV-1Tg rats compared with F344 rats. Further, more addiction-related genes were significantly modulated by nicotine in each brain region in the HIV-1Tg rats than in the control animals.ConclusionsHIV-1 proteins may affect novelty-seeking behavior and modulate the expression of genes related to drug addiction and novelty-seeking behavior.ImplicationsHIV-1 viral proteins and chronic nicotine treatment impact the expression of genes involved in novelty-seeking behavior and addiction in three brain regions of the HIV-1 transgenic rat. These findings implicate that HIV-1 proteins may be involved in novelty-seeking behavior and in modulating the expression of genes related to drug addiction and novelty seeking.