Xu Ming
Department of Cell Biology, Neurobiology and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.
Ann N Y Acad Sci. 1998 May;844(1):27-39. doi: 10.1111/j.1749-6632.1998.tb08219.x.
The dopamine D receptor is expressed mostly in the limbic regions of the brain that influence reward-related behaviors, including responses to psychostimulants. However, the lack of ligands with sufficient D receptor specificity has hampered our understanding of its possible involvement in mediating psychostimulant actions. To unravel dopamine D receptor function and underlying mechanisms in response to psychostimulants, we used a genetic approach and generated D receptor gene mutant mice. Our analysis indicates that the D mutant mice exhibit enhanced behavioral sensitivity to cocaine, amphetamine and combined injections of D- and D-class receptor agonists. By contrast, the combined electrophysiological effects of the same D- and D-class agonists on single neurons within the nucleus accumbens were not changed in the D mutant mice. We propose that the D receptor modulates responses to psychostimulants by inhibiting the cooperative effects of postsynaptic D- and other D-class receptors at systems level. The continuous use of the gene targeting approach will provide essential information regarding the molecular and cellular basis of psychostimulant actions and allow the development of new strategies in the prevention and cure of drug abuse.
多巴胺D受体主要表达于大脑的边缘区域，这些区域影响与奖赏相关的行为，包括对精神兴奋剂的反应。然而，缺乏具有足够D受体特异性的配体阻碍了我们对其可能参与介导精神兴奋剂作用的理解。为了阐明多巴胺D受体在对精神兴奋剂反应中的功能和潜在机制，我们采用了基因方法，培育出了D受体基因敲除小鼠。我们的分析表明，D基因敲除小鼠对可卡因、苯丙胺以及D类和D类受体激动剂联合注射表现出增强的行为敏感性。相比之下，相同的D类和D类激动剂对伏隔核内单个神经元的联合电生理效应在D基因敲除小鼠中并未改变。我们提出，D受体通过在系统水平上抑制突触后D受体和其他D类受体的协同作用来调节对精神兴奋剂的反应。持续使用基因靶向方法将提供有关精神兴奋剂作用的分子和细胞基础的重要信息，并有助于开发预防和治疗药物滥用的新策略。
