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首页> 外文期刊>Neuropsychopharmacology >Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice
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Contributions of Dopamine D1, D2, and D3 Receptor Subtypes to the Disruptive Effects of Cocaine on Prepulse Inhibition in Mice

机译：多巴胺D1，D2和D3受体亚型对可卡因对小鼠前脉冲抑制的破坏作用的贡献。

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Deficits in prepulse inhibition (PPI) of startle, an operational measure of sensorimotor gating, are characteristics of schizophrenia and related neuropsychiatric disorders. Previous studies in mice demonstrate a contribution of dopamine (DA) D1-family receptors in modulating PPI and DA D2 receptors (D2R) in mediating the PPI-disruptive effects of amphetamine. To examine further the contributions of DA receptor subtypes in PPI, we used a combined pharmacological and genetic approach. In congenic C57BL/6 J wild-type mice, we tested whether the D1R antagonist SCH23390 or the D2/3R antagonist raclopride would attenuate the effects of the indirect DA agonist cocaine (40?mg/kg). Both the D1R and D2/3R antagonists attenuated the cocaine-induced PPI deficit. We also tested the effect of cocaine on PPI in wild-type and DA D1R, D2R, or D3R knockout mice. The cocaine-induced PPI deficit was influenced differently by the three DA receptor subtypes, being absent in D1R knockout mice, partially attenuated in D2R knockout mice, and exaggerated in D3R knockout mice. Thus, the D1R is necessary for the PPI-disruptive effects of cocaine, while the D2R partially contributes to these effects. Conversely, the D3R appears to inhibit the PPI-disruptive effects of cocaine. Uncovering neural mechanisms involved in PPI will further our understanding of substrates of sensorimotor gating and could lead to better therapeutics to treat complex cognitive disorders such as schizophrenia.
机译：惊吓的脉冲前抑制（PPI）缺乏是感觉运动门控的一种手术措施，是精神分裂症和相关神经精神疾病的特征。小鼠先前的研究表明，多巴胺（DA）D1家族受体在调节PPI和DA D2受体（D2R）介导苯丙胺对PPI的破坏作用中发挥了作用。为了进一步检查DA受体亚型在PPI中的作用，我们使用了组合的药理和遗传方法。在同基因的C57BL / 6 J野生型小鼠中，我们测试了D1R拮抗剂SCH23390或D2 / 3R拮抗剂雷洛必利会减弱间接DA激动剂可卡因（40？mg / kg）的作用。 D1R和D2 / 3R拮抗剂均可减轻可卡因诱导的PPI缺乏。我们还测试了可卡因对野生型和DA D1R，D2R或D3R敲除小鼠中PPI的影响。可卡因诱导的PPI缺陷受三种DA受体亚型的影响不同，在D1R基因敲除小鼠中不存在，在D2R基因敲除小鼠中部分减弱，在D3R基因敲除小鼠中夸大。因此，D1R对于可卡因的PPI破坏作用必不可少，而D2R则在一定程度上促进了这些作用。相反，D3R似乎抑制可卡因的PPI破坏作用。揭示参与PPI的神经机制将进一步使我们对感觉运动门控的底物有所了解，并可能导致更好的疗法来治疗诸如精神分裂症等复杂的认知障碍。

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