Serotonergic genetic influences on the impact of maternal environment

血清素能遗传对母体环境的影响

基本信息

项目摘要

DESCRIPTION (provided by applicant): Susceptibility to neurobehavioral disorders, temperament, and stress responses arise from a complex interplay between genetic endowment and environmental factors, such as the mother/infant interaction. In both humans and rodent models, mother/infant interactions have been demonstrated to produce long-term effects on stress responsiveness, anxiety-like behavior and psychostimulant response. Many of these effects are thought to result from influences on the development and function of central dopamine systems. The availability of serotonin 5-HT2C receptor mutant mice affords a unique opportunity to dissect the role of the serotonin neurotransmitter system in influencing gene/environment interactions on neural substrates of stress responses and dopaminergic neurotransmission. Serotonin 5-HT2C receptor mutants exhibit alterations in the regulation of maternal behavior, novelty responses and enhanced dopaminergic neurotransmission (Preliminary Results). This proposal will test the hypothesis that the 5-HT2C receptor is an important mediator of serotonergic influences on mother/infant interactions and their long-term impact on offspring behavior. The proposal consists of three specific aims: Aim 1. Examination of the effects of a 5- HT2C receptor null mutation on maternal and pup behavior. Aim 2. Examination of the influence of maternal and offspring serotonin 5-HT2C receptor genotype on neural substrates of offspring stress responsiveness. This will be examined through fostering studies in which wild type and mutant pups are fostered to wild type, heterozygous and homozygous mutant mothers. Adult offspring will be examined using neuroendocrine, neuroanatomical and behavioral approaches. Aim 3. Examination of the influence of maternal and offspring 5-HT2C receptor genotype on offspring dopamine system function. Several approaches will be applied to examine central dopamine systems in adult offspring of the fostering groups described in Aim 2. Neuroanatomical assessment of genes implicated dopaminergic neurotransmission will be performed, and in vivo microdialysis procedures will be used to assess extracellular dopamine levels in awake, behaving mice.
描述(由申请人提供):对神经行为障碍、气质和应激反应的易感性源于遗传禀赋和环境因素(如母婴相互作用)之间的复杂相互作用。在人类和啮齿动物模型中,母亲/婴儿的相互作用已被证明对应激反应、焦虑样行为和精神兴奋反应产生长期影响。许多这些影响被认为是由于对中枢多巴胺系统的发育和功能的影响。5-羟色胺5-HT 2C受体突变小鼠的可用性提供了一个独特的机会,剖析5-羟色胺神经递质系统的作用,在影响基因/环境相互作用的神经底物的应激反应和多巴胺能神经传递。5-羟色胺5-HT 2C受体突变体在母体行为调节、新奇反应和增强的多巴胺能神经传递方面表现出改变(初步结果)。该提案将测试的假设,即5-HT 2C受体是一个重要的介导的雌激素能影响母亲/婴儿的相互作用和他们的长期影响后代的行为。该提案包括三个具体目标:目标1。检查5-HT 2C受体无效突变对母体和幼仔行为的影响。目标二。母亲和后代5-羟色胺5-HT 2C受体基因型对后代应激反应性神经底物的影响的检查。这将通过寄养研究进行检查,其中野生型和突变型幼仔被寄养给野生型、杂合和纯合突变型母体。将使用神经内分泌、神经解剖和行为方法检查成年后代。目标3.母亲和后代5-HT 2C受体基因型对后代多巴胺系统功能的影响的检查。几种方法将被应用于检查中央多巴胺系统中的成年后代的寄养组中描述的目标2。将进行涉及多巴胺能神经传递的基因的神经解剖学评估,并将使用体内微透析程序来评估清醒的行为小鼠中的细胞外多巴胺水平。

项目成果

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Laurence H. Tecott其他文献

Laurence H. Tecott的其他文献

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{{ truncateString('Laurence H. Tecott', 18)}}的其他基金

Striatal Circuits In The Serotonergic Modulation Of Hedonic States
享乐状态的血清素调节中的纹状体回路
  • 批准号:
    8889134
  • 财政年份:
    2015
  • 资助金额:
    $ 18.91万
  • 项目类别:
Striatal Circuits In The Serotonergic Modulation Of Hedonic States
享乐状态的血清素调节中的纹状体回路
  • 批准号:
    9139502
  • 财政年份:
    2015
  • 资助金额:
    $ 18.91万
  • 项目类别:
Impact of energy status on the serotonergic regulation of energy balance
能量状态对能量平衡的血清素调节的影响
  • 批准号:
    7992350
  • 财政年份:
    2010
  • 资助金额:
    $ 18.91万
  • 项目类别:
Impact of Energy Status on the Serotonergic Regulation of Energy Balance
能量状态对能量平衡的血清素调节的影响
  • 批准号:
    8309292
  • 财政年份:
    2010
  • 资助金额:
    $ 18.91万
  • 项目类别:
Impact of energy status on the serotonergic regulation of energy balance
能量状态对能量平衡的血清素调节的影响
  • 批准号:
    8129661
  • 财政年份:
    2010
  • 资助金额:
    $ 18.91万
  • 项目类别:
Impact of Energy Status on the Serotonergic Regulation of Energy Balance
能量状态对能量平衡的血清素调节的影响
  • 批准号:
    8499295
  • 财政年份:
    2010
  • 资助金额:
    $ 18.91万
  • 项目类别:
Management and Analysis of Mouse Behavioral Datasets
小鼠行为数据集的管理和分析
  • 批准号:
    7211528
  • 财政年份:
    2007
  • 资助金额:
    $ 18.91万
  • 项目类别:
A Quantitative Approach for Detecting Anxiolytic Drug Effects in the Mouse
检测小鼠抗焦虑药物作用的定量方法
  • 批准号:
    7486179
  • 财政年份:
    2007
  • 资助金额:
    $ 18.91万
  • 项目类别:
Management and Analysis of Mouse Behavioral Datasets
小鼠行为数据集的管理和分析
  • 批准号:
    7540463
  • 财政年份:
    2007
  • 资助金额:
    $ 18.91万
  • 项目类别:
A Quantitative Approach for Detecting Anxiolytic Drug Effects in the Mouse
检测小鼠抗焦虑药物作用的定量方法
  • 批准号:
    7305447
  • 财政年份:
    2007
  • 资助金额:
    $ 18.91万
  • 项目类别:

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