High and low doses of cocaine intake are differentially regulated by dopamine D2 receptors in the ventral tegmental area and the nucleus accumbens.
High and low doses of cocaine intake are differentially regulated by dopamine D2 receptors in the ventral tegmental area and the nucleus accumbens.
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DOI：
10.1016/j.neulet.2018.02.026
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发表时间：
2018-04-03
影响因子：
2.5
通讯作者：
Childers SR
中科院分区：
文献类型：
--
作者：
Chen R;McIntosh S;Hemby SE;Sun H;Sexton T;Martin TJ;Childers SR
腹侧被盖区 (VTA) 和伏隔核 (NAc) 中的多巴胺 D2 受体 (D2R) 与成瘾易感性相关；然而，这两个大脑区域的 D2R 在药物摄入调节中是否发挥不同的作用尚不清楚。在这里，我们在剂量反应函数中比较了每个区域 Drd2 mRNA 水平降低对可卡因自我给药的影响。通过双侧显微注射针对大鼠 Drd2 的慢病毒编码 shRNA，可降低大鼠 VTA 或 NAc 中的 Drd2 mRNA 水平。 Drd2 敲低在慢病毒感染后 20 至 90 天内持续稳定。 Drd2 shRNA 治疗后 20 天，训练动物自行施用可卡因。与乱序shRNA治疗的大鼠相比，VTA中的Drd2敲除增加了所有测试剂量（0.02-0.56 mg/kg/输注）的可卡因自我给药，产生可卡因自我给药的剂量反应曲线的向上移动（上升和下降肢体）。相比之下，NAc内敲低仅在剂量反应曲线的上升部分增加了可卡因的自我给药（0.02-0.07 mg/kg/输注）。这些数据表明，VTA 中的 D2R（而不是 NAc 中）调节高剂量可卡因的摄入。本研究不仅证明任一区域的低水平 D2R 会增加低剂量可卡因摄入量，而且首次揭示了它们在限制高剂量可卡因自我给药方面的分离作用。
Dopamine D2 receptors (D2Rs) in the ventral tegmental area (VTA) and the nucleus accumbens (NAc) are associated with vulnerability to addiction; however, whether D2Rs in these two brain regions play differential roles in regulation of drug intake is unknown. Here, we compared the effect of decreased mRNA level of Drd2 in each region on cocaine self-administration in a dose-response function. Drd2 mRNA levels in rat VTA or NAc were knocked down by bilateral microinjection of lentivirus coding shRNAs against rat Drd2. Drd2 knockdown was persistent and stable between 20 and 90 days after lentiviral infection. Animals were trained to self-administer cocaine 20 days after Drd2 shRNA treatment. Compared to scrambled shRNA treated rats, Drd2 knockdown in the VTA increased cocaine self-administration at all tested doses (0.02-0.56 mg/kg/infusion) producing an upward shift (both the ascending and descending limb) in the dose-response curve of cocaine self-administration. In contrast, intra-NAc knockdown increased cocaine self-administration only on the ascending limb of the dose-response curve (0.02-0.07 mg/kg/infusion). These data suggest that D2Rs in the VTA, not in the NAc, regulate high-dose cocaine intake. The present study not only demonstrates that low levels of D2Rs in either region increase low doses of cocaine intake, but also reveals for the first time their dissociable roles in limiting high doses of cocaine self-administration.
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影响因子：
3.5
作者：
Baik JH
通讯作者：
Baik JH
影响因子：
25
作者：
Bock, Roland;Shin, J. Hoon;Kaplan, Alanna R.;Dobi, Alice;Markey, Eric;Kramer, Paul F.;Gremel, Christina M.;Christensen, Christine H.;Adrover, Martin F.;Alvarez, Veronica A.
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影响因子：
6.8
作者：
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通讯作者：
Mickey BJ
DOI：
10.1523/jneurosci.4287-10.2011
发表时间：
2011-01-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
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作者：
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通讯作者：
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影响因子：
3.4
作者：
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通讯作者：
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