Ventral tegmental area D2 receptor knockdown enhances choice impulsivity in a delay-discounting task in rats.
Ventral tegmental area D2 receptor knockdown enhances choice impulsivity in a delay-discounting task in rats.
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DOI：
10.1016/j.bbr.2017.12.029
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发表时间：
2018-04-02
影响因子：
2.7
通讯作者：
Bass CE
中科院分区：
文献类型：
--
作者：
Bernosky-Smith KA;Qiu YY;Feja M;Lee YB;Loughlin B;Li JX;Bass CE
与多巴胺(DA)功能异常相关的冲动在几种疾病中都被观察到，包括成瘾。选择冲动是指，由于对未来奖励的过度贴现，在延迟一段时间后，相对于较大的奖励，选择冲动更倾向于立即获得小额奖励。瘾君子有异常高的折扣率，他们更喜欢更快获得较小的回报。虽然冲动性与中脑和纹状体中DA D2受体(D2R)的可获得性呈负相关，但由于D2R在大脑中的不同神经解剖学定位，在许多类型的神经元和神经元亚室中都发现了D2R，因此很难将两者联系起来。为了确定腹侧被盖区(VTA)D2R功能低下是否与冲动有关，我们用腺相关病毒(AAV)载体携带针对D2R的短发夹状RNA(ShRNA)，从VTA中敲除了D2受体。D2R基因敲除仅限于其胞体位于VTA的神经元，而纹状体、前额叶皮质和其他中皮质边缘结构中的突触后D2Rs保持不变。训练大鼠进行延迟折扣任务，以评估冲动选择，直到获得稳定的折扣曲线，然后接受双侧VTA注射D2R shRNA或扰乱的对照病毒。在接下来的六周里，VTA D2R基因敲除大鼠的贴现曲线左移，表明更倾向于较小的即时奖励，而对照组大鼠的曲线保持稳定和不变。综上所述，这些结果表明，VTA D2受体的减少会增强选择冲动。
Impulsivity associated with abnormal dopamine (DA) function has been observed in several disorders, including addiction. Choice impulsivity is the preference for small, immediate rewards over larger rewards after a delay, caused by excessive discounting of future rewards. Addicts have abnormally high discount rates and prefer the smaller rewards sooner. While impulsivity has been inversely correlated with DA D2 receptor (D2R) availability in the midbrain and striatum, it is difficult to mechanistically link the two, due to the diverse neuroanatomical localization of D2Rs, which are found throughout the brain, in many types of neurons and neuronal subcompartments. To determine if ventral tegmental area (VTA) D2R hypofunction is linked to impulsivity, we knocked down D2 receptors from the VTA, using an adeno-associated viral (AAV) vector that delivers short hairpin RNAs (shRNA) targeted against the D2R. The D2R knockdown is restricted to neurons whose cell bodies reside in the VTA, leaving postsynaptic D2Rs intact in the striatum, prefrontal cortex, and other mesocorticolimbic structures. Rats were trained in a delay-discounting task to assess impulsive choice until a stable discounting curve was obtained, and then received bilateral VTA infusions of the D2R shRNA or a scrambled control virus. Over the next six weeks, the discounting curve of the VTA D2R knockdown rats shifted to the left, indicating a preference for the smaller, immediate reward, whereas the curve for control rats remained stable and unchanged. Together these results demonstrate that a decrease in VTA D2 receptors enhances choice impulsivity.
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影响因子：
12.4
作者：
Cearley, CN;Wolfe, JH
通讯作者：
Wolfe, JH
DOI：
10.1016/j.cub.2016.11.029
发表时间：
2017-01-09
期刊：
Current biology : CB
影响因子：
--
作者：
Kim YC;Han SW;Alberico SL;Ruggiero RN;De Corte B;Chen KH;Narayanan NS
通讯作者：
Narayanan NS
影响因子：
3
作者：
Bass CE;Grinevich VP;Gioia D;Day-Brown JD;Bonin KD;Stuber GD;Weiner JL;Budygin EA
通讯作者：
Budygin EA
影响因子：
6.8
作者：
Joutsa J;Voon V;Johansson J;Niemelä S;Bergman J;Kaasinen V
通讯作者：
Kaasinen V
影响因子：
5.2
作者：
Jentsch JD;Ashenhurst JR;Cervantes MC;Groman SM;James AS;Pennington ZT
通讯作者：
Pennington ZT