Analysis of 5-HT6 and 5-HT7 receptor gene expression in rats showing differences in novelty-seeking behavior
Analysis of 5-HT6 and 5-HT7 receptor gene expression in rats showing differences in novelty-seeking behavior
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DOI：
10.1016/j.neuroscience.2007.04.024
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发表时间：
2007-06-29
期刊：
影响因子：
3.3
通讯作者：
Watson, S. J.
中科院分区：
文献类型：
--
作者：
Ballaz, S. J.;Akil, H.;Watson, S. J.
感觉寻求是一种与使用精神活性物质的更大倾向相关的人类人格特征。已经开发出一种显示这种人类特征的表面有效性的大鼠模型。该模型是基于大鼠在一个新的和不可避免的环境中表现出的各种行为反应，其中一些动物（高反应者，HR）非常活跃，而其他动物（低反应者，LR）表现出较少的探索。更活跃的大鼠（HR）也表现出增加的药物摄入和减少的焦虑样行为。有证据表明，对新奇事物的反应可能依赖于不同的5-HT介导的神经传递。本研究的重点是最近发现的5-HT 6和5-HT 7受体，这些受体对神经安定药物和致幻剂具有亲和力。到目前为止，新的证据表明，5-HT 6和5-HT 7可能分别参与认知和情绪调节。为了进一步了解它们的行为属性，我们比较了HR和LR大鼠大脑中这些受体的基因表达模式。作为对照，研究了5-HT 3受体的基因表达，因为它对焦虑和成瘾的贡献仅得到微弱的证明。嗅结节中5-HT 6的转录水平与新环境中的运动水平呈负相关。5-HT 6 mRNA信号的表型差异在齿状回中表现出复杂的模式。LR大鼠在齿状回的最前部区域具有统计学意义，而HR大鼠在齿状回的中间区域具有统计学意义。HR大鼠在丘脑-皮质投射区和背侧海马等信息传递的关键区域5-HT 7转录水平显著低于LR大鼠。相比之下，5-HT 3表达的表型差异没有发现在边缘皮质和中脑边缘系统的地区。总之，这些结果为5-HT对新奇寻求行为和相关行为（如药物滥用）的潜在贡献提供了新的见解。由Elsevier Ltd代表IBRO出版。
Sensation-seeking is a human personality trait associated with a greater propensity to use psychoactive substances. A rat model showing face validity of this human trait has been developed. The model is based on the variety of behavioral responses that rats exhibit in a novel and inescapable environment, with some animals (high-responders, HR) being highly active, and others (low-responders, LR) showing less exploration. More active rats (HR) also show increased drug-taking and decreased anxiety-like behavior. There is evidence that response to novelty may rely on differential 5-HT-mediated neurotransmission. This research focuses on the recently discovered 5-HT6 and 5-HT7 receptors which share affinity for neuroleptic drugs and hallucinogens. To date, emerging evidence suggests that 5-HT6 and 5-HT7 may be involved in cognition and mood regulation, respectively. To further our knowledge of their behavioral attributes, we compared patterns of gene expression for these receptors in the brains of HR and LR rats. As a control, gene expression for the 5-HT3 receptor was investigated because its contribution to anxiety and addiction is only weakly demonstrated. Transcript levels for 5-HT6 in the olfactory tubercle inversely correlated with the level of locomotion in a novel environment. Phenotype differences in mRNA signal for 5-HT6 showed a complex pattern in the dentate gyrus. LR rats were statistically higher in the most anterior region of the dentate gyrus, while HR rats were higher in median areas of the dentate gyrus. Levels of 5-HT7 transcript in HR rats were significantly lower than LR rats in pivotal areas for information trafficking, such as thalamo-cortical projection areas and dorsal hippocampus. By contrast, phenotype differences in 5-HT3 expression were not found in areas of the limbic cortex and mesolimbic system. Taken together, these results provide new insight into the potential contribution of 5-HT to novelty-seeking behavior and associated behaviors such as substance abuse. Published by Elsevier Ltd on behalf of IBRO.