在腹膜区域的胺基H3调节可卡因寻找
Ashley E Lepack1, Craig T Werner2, Andrew F Stewart1
1Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
概括
可卡因成通过基因修饰改变大脑基因表达. 在腹膜区域 (VTA) 降低基因组H3胺5多巴化 (H3Q5dop) 可逆转这些变化,并减少了可卡因寻找.
科学领域:
- 神经科学
- 分子生物学
- 关于成的研究
背景情况:
- 可卡因成与大脑奖励通路的变化有关, 尤其是腹膜区域 (VTA) 的多巴胺神经元.
- 可卡因改变中脑多巴胺神经元的基因表达的确切机制,
研究的目的:
- 调查中脑中可卡因诱导的转录变化中的基因组修饰的作用.
- 确定基因组H3胺5多巴化 (H3Q5dop) 是否与可卡因成和复发行为有关.
主要方法:
- 使用一种老鼠吸毒模式.
- 在VTA中测量素H3胺5多巴化 (H3Q5dop) 水平.
- 在戒断期间进行干预措施以降低VTA中的H3Q5dop.
- 分析了基因表达的变化,核中多巴胺的释放, 和寻找可卡因的行为.
主要成果:
- 可卡因戒断导致VTA中的H3Q5dop积累增加.
- 减少VTA中的H3Q5dop可以逆转与可卡因相关的基因表达变化.
- 干预也减轻了核中多巴胺的释放,并减少了寻找可卡因的行为.
结论:
- 在VTA中可卡因诱导的转录可塑性中,素H3胺5多巴化 (H3Q5dop) 是至关重要的.
- 核多巴胺独立于神经传递,在与成相关的基因表达和复发行为中起重要作用.
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