Gainetdinov Raul R, Sotnikova Tatyana D, Caron Marc G
Howard Hughes Medical Institute Laboratories, Dept of Cell Biology, Box 3287, Duke University Medical Center, Durham, NC 27710, USA.
Trends Pharmacol Sci. 2002 Aug;23(8):367-73. doi: 10.1016/s0165-6147(02)02044-8.
Monoamine transporters, such as the dopamine transporter, 5-HT transporter and noradrenaline transporter, in the plasma membrane provide effective control over the intensity of monoamine-mediated signaling by recapturing neurotransmitters released by presynaptic neurons. These proteins represent established targets for several psychotropic drugs, including psychostimulants and antidepressants; however, important issues regarding the selectivity and mechanisms of action of these drugs remain unresolved. Although monoamine transporter knockout mice have profound changes in neurotransmission, they provide useful in vivo models to analyze the effects of psychotropic drugs. In this review, we summarize recent insights into the pharmacology of psychotropic drugs using mice in which the genes encoding these transporters have been deleted.
质膜中的单胺转运体,如多巴胺转运体、5-羟色胺转运体和去甲肾上腺素转运体,通过重新摄取突触前神经元释放的神经递质,对单胺介导的信号强度进行有效控制。这些蛋白质是包括精神兴奋剂和抗抑郁药在内的几种精神药物的既定靶点;然而,关于这些药物的选择性和作用机制的重要问题仍未得到解决。尽管单胺转运体基因敲除小鼠的神经传递有深刻变化,但它们为分析精神药物的作用提供了有用的体内模型。在这篇综述中,我们总结了使用缺失编码这些转运体基因的小鼠对精神药物药理学的最新见解。