Relative expression of D3 dopamine receptor and alternative splice variant D3nf rnRNA in high and low responders to novelty
Relative expression of D3 dopamine receptor and alternative splice variant D3nf rnRNA in high and low responders to novelty
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DOI：
10.1016/j.brainresbull.2006.06.010
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发表时间：
2006-10-16
影响因子：
3.8
通讯作者：
Richtand, Neil M.
中科院分区：
文献类型：
--
作者：
Pritchard, Laurel M.;Logue, Aaron D.;Richtand, Neil M.
对啮齿动物的研究表明，D3多巴胺受体在调节对空间新奇事物和精神刺激剂的运动反应中起着重要作用。D3受体选择性剪接变异体D3nf产生一种非多巴胺结合蛋白，该蛋白可能通过与全长受体二聚体改变D3受体的定位。在高响应者/低响应者(HR/LR)模型中，对不可避免的、新颖的空间环境的运动反应预测了运动的个体差异和心理刺激剂的奖励效应。我们假设，在HR/LR模型中，D3受体表达的个体差异可能导致对新奇事物的运动反应的个体差异。为了验证这一假设，我们筛选了大鼠对新的空间环境的反应，并通过实时RT-PCR分析了脑组织D3受体和D3nf的mRNA水平。HRS组前额叶皮质和黑质/腹侧被盖D3/D3nf mRNA的比值明显低于LRS组。D3/D3nf在伏隔核中的相对表达在HRs和LRs之间没有差异。这些数据进一步支持D3多巴胺受体在新颖性行为反应中的作用，并鉴于新颖性和心理刺激反应之间已建立的关系，表明D3受体可能是评估药物滥用易感性的重要靶标。此外，这些发现与选择性剪接可能有助于调节D3多巴胺受体功能的假设是一致的。(C)2006 Elsevier Inc.保留所有权利。
Studies in rodents suggest an important role for the D3 dopamine receptor in regulating locomotor responses to spatial novelty and psychostimulants. The D3 receptor alternatively spliced variant D3nf produces a non-dopamine binding protein that may alter D3 receptor localization by dimerizing with the full-length receptor. In the high responder/low responder (HR/LR) model, the locomotor response to an inescapable, novel spatial environment predicts individual differences in the locomotor and rewarding effects of psychostimulants. We hypothesized that individual differences in D3 receptor expression could contribute to individual differences in the locomotor response to novelty in the HR/LR model. To test this hypothesis, we screened rats for response to a novel spatial environment and analyzed brain tissue for mRNA levels of the D3 receptor and D3nf by real-time RT-PCR. The ratios of D3/D3nf mRNA in prefrontal cortex and substantia nigra/ventral tegmentum were significantly lower in HRs than in LRs. There were no differences in relative expression of D3/D3nf between HRs and LRs in nucleus accumbens. These data further support a role for the D3 dopamine receptor in behavioral responses to novelty and, given the established relationship between novelty and psychostimulant responses, suggest that the D3 receptor may be an important target for assessment of drug abuse vulnerability. Additionally, these findings are consistent with the hypothesis that alternative splicing may contribute to regulation of D3 dopamine receptor function. (c) 2006 Elsevier Inc. All rights reserved.