There's no place like home? Return to the home cage triggers dopamine release in the mouse nucleus accumbens.

There's no place like home? Return to the home cage triggers dopamine release in the mouse nucleus accumbens.
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DOI:
10.1016/j.neuint.2020.104894
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发表时间:
2021-01
影响因子:
4.2
通讯作者:
Blakely RD
Blakely RD
中科院分区:
医学3区
文献类型:
--
作者:
Mayer FP;Iwamoto H;Hahn MK;Grumbar GJ;Stewart A;Li Y;Blakely RD

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在临床前啮齿动物模型中,各种刺激被用作增强剂,在分子和电路水平上阐明奖赏的基础,伏隔核多巴胺(DA)的释放是一种复制良好的生理关联。然而,许多因素,包括品系差异、性别、先前的压力和增强剂给药方案,都会影响奖励反应和DA释放。尽管先前的证据表明,接触家庭笼子可以有效地增强行为任务,但这种简单的环境操纵是否可以触发NAC中DA的释放还没有得到证实。在这里,使用从遗传编码的DA传感器体内NAC多巴胺释放的光纤光度记录,我们表明,动物从家庭笼子到透明的聚碳酸酯记录室的运动在最初暴露后几乎没有引起DA释放,而将动物从记录室返回到干净的类似家庭的笼子或家庭笼子强烈地触发DA的释放,其大小与观察到的10 mg/kg ip相当。在录音室注射可卡因。虽然把小鼠移到干净的笼子里可以引起DA的释放,但当把动物从干净的笼子移到家里的笼子里时,这种释放明显增加。我们的数据提供了直接证据,证明从外国环境返回的家笼会导致与奖励刺激一致的生化变化。这种简单的环境操作提供了一种微创的方法来研究与行为学相关的增强剂背后的奖励电路,返回安全的家。家庭笼式DA释放范式也可以代表一种生物标记物驱动的范式,用于评估构成主要情绪障碍特征的享乐状态的遗传和经验事件,并提供新的机会来确定其治疗方法。
Various stimuli have been employed as reinforcers in preclinical rodent models to elucidate the underpinnings of reward at a molecular and circuit level, with the release of dopamine (DA) in the nucleus accumbens (NAc) as a well-replicated, physiological correlate. Many factors, however, including strain differences, sex, prior stress, and reinforcer administration protocols can influence reward responding and DA release. Although previous evidence indicates that access to the home cage can be an effective reinforcer in behavioral tasks, whether this simple environmental manipulation can trigger DA release in the NAc has not been demonstrated. Here, using fiber photometric recordings of in vivo NAc dopamine release from a genetically-encoded DA sensor, we show that the movement of animals from the home cage to a clear, polycarbonate recording chamber evokes little to no DA release following initial exposure whereas returning animals from the recording chamber to a clean, home-like cage or to the home cage robustly triggers the release of DA, comparable in size to that observed with a 10 mg/kg i.p. cocaine injection in the recording chamber. Although DA release can be evoked in moving mice to a clean cage, this release was significantly augmented when moving animals from the clean cage to the home cage. Our data provide direct evidence that home cage return from a foreign environment results in a biochemical change consistent with that of a rewarding stimulus. This simple environmental manipulation provides a minimally invasive approach to study the reward circuitry underlying an ethologically relevant reinforcer, return to the safe confines of “home”. The home cage – DA release paradigm may also represent a biomarker-driven paradigm for the evaluation of genetic and experiential events that underlie anhedonic states, characteristic of major mood disorders, and to present new opportunities to identify their treatments.
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发表时间: 2014-01
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发表时间: 2010-05-22
期刊: Journal of visualized experiments : JoVE
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