Viral over-expression of D1 dopamine receptors in the prefrontal cortex increase high-risk behaviors in adults: comparison with adolescents.
Viral over-expression of D1 dopamine receptors in the prefrontal cortex increase high-risk behaviors in adults: comparison with adolescents.
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DOI：
10.1007/s00213-013-3399-8
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发表时间：
2014-04
影响因子：
3.4
通讯作者：
Andersen, Susan L.
中科院分区：
文献类型：
--
作者：
Sonntag, Kai C.;Brenhouse, Heather C.;Freund, Nadja;Thompson, Britta S.;Puhl, Matthew;Andersen, Susan L.
青少年经常被描述为“缺乏刹车”，导致与成瘾风险相关的几种行为增加。前额叶皮质多巴胺和皮质-边缘相互作用在成瘾中起重要作用，我们先前的研究表明，在青春期大鼠的前额叶输出神经元上，多巴胺D1受体升高。我们假设，一系列与风险相关的行为是由前额叶输出神经元D1的表达所介导的。我们的目的是确定多巴胺D1受体在青少年经常观察到的成瘾风险的行为和神经相关中所起的作用。因此，我们研究了前额叶谷氨酸能神经元D1值升高的成年动物的高危行为和皮质下D2受体的表达。将选择性表达D_1受体的慢病毒载体注射到成年雄性大鼠的前额叶皮质。对可卡因、酒精和尼古丁的条件作用以及延迟折扣、新奇偏好、焦虑、可卡因自我管理和蔗糖偏好进行了评估。病毒介导的D1在成人中的过度表达会导致更强的药物线索联系，更多的甜味溶液的消费，提高对即时满足而不是延迟满足的偏见，减少焦虑，并导致大鼠更加努力地争取和服用更多的可卡因。此外，皮质D1值升高会减少伏隔核中的D2受体(一种可能的危险标记)。综上所述，这些数据表明了一种共同的机制，即增强动机动力，寻找和消费具有享乐价值的物质，与青少年成瘾过程一致。
Adolescents are often described as “lacking brakes” resulting in an increase in several behaviors associated with risk for addiction. Prefrontal cortex dopamine and cortico-limbic interaction play an important role in addiction, and we have previously shown that the dopamine D1 receptor is elevated on prelimbic prefrontal output neurons in adolescent rats. We hypothesized that a constellation of risk-related behaviors are mediated by prefrontal output neuron expression of D1. We aimed to determine the role of the dopamine D1 receptor in behavioral and neural correlates of risk for addiction that are often observed in adolescents. Therefore high-risk behaviors as well as subcortical D2 receptor expression were investigated in adult animals with experimentally elevated D1 on prefrontal glutamatergic neurons. A lentiviral vector that selectively expressed the D1 receptor within glutamate neurons was injected in the prelimbic prefrontal cortex of adult male rats. Place conditioning to cocaine, alcohol, and nicotine, as well as delay discounting, novelty preferences, anxiety, cocaine self-administration, and sucrose preferences were assessed. Virally-mediated D1 overexpression in adults leads to stronger drug-cue associations, greater consumption of sweet solutions, elevates bias towards immediate satisfaction rather than delaying gratification, decreases anxiety and causes rats to work harder for and take more cocaine. Furthermore elevated cortical D1 reduces D2 receptors in the accumbens (a putative risk marker). Together, these data suggest a common mechanism for increased motivational drive to seek and consume substances with hedonic value, consistent with adolescent addictive processes.
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影响因子：
64.8
作者：
Flagel SB;Clark JJ;Robinson TE;Mayo L;Czuj A;Willuhn I;Akers CA;Clinton SM;Phillips PE;Akil H
通讯作者：
Akil H
影响因子：
10.6
作者：
Diergaarde, Leontien;Pattij, Tommy;De Vries, Taco J.
通讯作者：
De Vries, Taco J.
影响因子：
3.6
作者：
Anker, Justin J.;Perry, Jennifer L.;Gliddon, Luke A.;Carroll, Marilyn E.
通讯作者：
Carroll, Marilyn E.
影响因子：
7.6
作者：
Frantz, Kyle J.;O'Dell, Laura E.;Parsons, Loren H.
通讯作者：
Parsons, Loren H.
影响因子：
8.2
作者：
Brenhouse, Heather C.;Andersen, Susan L.
通讯作者：
Andersen, Susan L.