Lack of β2-AR Increases Anxiety-Like Behaviors and Rewarding Properties of Cocaine.
Lack of β2-AR Increases Anxiety-Like Behaviors and Rewarding Properties of Cocaine.
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缺乏 β2-AR 会增加焦虑样行为和可卡因的奖励特性
DOI：
10.3389/fnbeh.2017.00049
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发表时间：
2017
影响因子：
3
通讯作者：
Liu X
中科院分区：
文献类型：
--
作者：
Zhu H;Liu Z;Zhou Y;Yin X;Xu B;Ma L;Liu X
众所周知，β-肾上腺素受体（β-ARs）在情绪唤醒和应激事件中起关键作用，但β2-AR亚型对心理障碍的具体贡献在很大程度上是未知的。为了研究β2-AR是否与焦虑样行为和成瘾药物奖励有关，我们对β2-AR敲除（KO）小鼠进行了一系列行为测试。β2-AR在光/暗盒和升高加迷宫实验中表现出对暗室和闭臂的偏好增加，表明β2-AR缺失提高了焦虑或先天恐惧水平。β2-AR KO小鼠在尾悬试验（TST）中也表现出不动性下降，表明β2-AR缺失抑制了抑郁样行为。有趣的是，β2-AR消融不改变基础运动，但显著增加急性可卡因诱导的运动活动。β2-AR KO小鼠对可卡因的位置偏好增强，β1选择性AR拮抗剂倍他洛尔可以减弱这种偏好。β2-AR激动剂抑制可卡因条件下的位置偏好（CPP）。这些数据表明β2-AR缺失增强了对可卡因的急性反应和奖励。我们的研究结果表明，β2-AR调节可卡因的焦虑水平、抑郁样行为和享乐特性，暗示β2-AR是治疗情绪障碍和可卡因成瘾的潜在靶点。
It is well known that β-adrenoceptors (β-ARs) play a critical role in emotional arousal and stressful events, but the specific contributions of the β2-AR subtype to the psychological disorders are largely unknown. To investigate whether β2-AR are involved in anxiety-like behavior and reward to addictive drugs, we conducted a series of behavioral tests on β2-AR knock-out (KO) mice. β2-AR KO mice exhibited increased preference for the dark compartment and closed arm in tests of Light/Dark box and elevated plus maze, indicating that β2-AR deletion elevates level of anxiety or innate fear. β2-AR KO mice also showed decreased immobility in tail suspension test (TST), suggesting that β2-AR deletion inhibits depression-like behavior. Interestingly, β2-AR ablation did not change basal locomotion but significantly increased locomotor activity induced by acute cocaine administration. β2-AR KO mice showed enhanced place preference for cocaine, which could be attenuated by β1-selective AR antagonist betaxolol. Consistently, β2-AR agonist suppressed cocaine-conditioned place preference (CPP). These data indicate that β2-AR deletion enhances acute response and reward to cocaine. Our results suggest that β2-AR regulates anxiety level, depression-like behavior and hedonic properties of cocaine, implicating that β2-AR are the potential targets for the treatment of emotional disorders and cocaine addiction.