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光遗传激活中枢杏仁核会产生类似成瘾的奖励偏好。

Optogenetic activation of the central amygdala generates addiction-like preference for reward.

机构信息

Neuroscience & Behavior Program, Wesleyan University, Middletown, Connecticut.

Dartmouth Geisel School of Medicine, Hanover, New Hampshire.

出版信息

Eur J Neurosci. 2019 Aug;50(3):2086-2100. doi: 10.1111/ejn.13967. Epub 2018 Jun 15.

Abstract

Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin-2 (ChR2). Rats developed an almost exclusive preference for the laser-paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation-paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (≈20%) retained an exclusive laser-paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction-like behaviour that persists in the face of more rewarding alternatives and adverse consequences.

摘要

药物和行为成瘾的特点是强烈而专注地追求单一的奖励,超过其他所有奖励。尽管有不良后果和更好的替代结果,对成瘾性奖励的追求往往还是强制性的。在这里,我们探索了中央杏仁核(CeA)有力地影响选择的能力,导致特定的奖励几乎被强迫性地偏好。大鼠在操作性选择任务中接受训练,在该任务中,它们可以选择在两个杠杆中的任何一个上做出反应以获得蔗糖奖励,其中一个与使用通道视紫红质-2(ChR2)对 CeA 的光遗传学刺激配对。大鼠对激光配对奖励的偏好几乎超过了其他同等的非配对奖励。我们发现,即使提供更大的蔗糖奖励作为替代(条件管理),或者当这种偏好的奖励与不良后果(如逐渐增大的电击、时间延迟或努力要求)配对时,这种对刺激配对奖励的偏好仍然存在。我们还报告说,当面临电击挑战时,这些动物中的一小部分(约 20%)保留了对激光配对奖励的排他性偏好,而其他动物则在电击达到高水平时开始寻求替代奖励。最后,我们确认如果在没有配对的蔗糖奖励的情况下给予光遗传学 CeA 刺激,则其本身并没有独立的奖励作用。这些结果表明 CeA 在将动机和欲望集中到过度水平方面起着作用,产生类似成瘾的行为,即使面对更有回报的替代方案和不良后果,这种行为也会持续存在。

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