缺少TAAR1功能会增加甲基胺诱导的背脊拉菲血清蛋白神经元的兴奋性,并驱动大量的甲基胺摄入量
Samantha M Rios1, John R K Mootz1, Tamara J Phillips1,2
1Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
概括
遗传因素影响甲基胺 (MA) 的摄入. 非功能性微量氨基关联受体1 (TAAR1) 通过通过血清素载体改变血清素神经元活动来增加MA奖励灵敏度和摄入量.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 甲基胺 (MA) 是一种精神兴奋剂,其摄入量因奖励和厌恶效应而变化.
- 影响MA敏感性的遗传因素对于开发有效治疗方法至关重要.
- 背脊拉菲赛洛托尼神经元活动与奖励处理有关.
研究的目的:
- 研究微氨基关联受体1 (TAAR1) 在MA奖励敏感性和摄入中的作用.
- 为了检查TAAR1功能对背脊拉菲血清激素神经元活动对MA的反应的影响.
- 为了阐明TAAR1和血清素载体在MA神经化学效应中的相互作用.
主要方法:
- 整个细胞补丁电生理学被用于从高 (MAHDR) 或低 (MALDR) MA摄入量小鼠的背脊拉菲血清激素神经元.
- MAHDR小鼠具有非功能性TAAR1 (Taar1m1J) 的突变,而MALDR小鼠具有功能性TAAR1 (Taar1+).
- 实验涉及单独使用MA和与血清素自身受体对抗剂或血清素输送剂对抗剂 (fluoxetine) 联合使用MA.
主要成果:
- 在MALDR小鼠中,MA降低了背脊拉菲类血清激素神经元活动,但不是MAHDR小鼠.
- 在对抗剂的存在下,MA在MAHDR小鼠中增强了血清神经元活性,这种效应在具有功能TAAR1.1的敲入小鼠中被废除了.
- 素阻断了非功能TAAR1的小鼠中的MA诱导的强化,这表明胺转运器参与.
结论:
- TAAR1的功能极大地调节了MA奖励的敏感性和摄入量.
- 非功能性TAAR1导致MA的消耗增加,因为它改变了MA对背部神经元的作用.
- TAAR1与血清素载体相互作用,调节MA诱导的神经元活动的变化.
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