Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior
Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior
复制标题
DOI：
10.1016/j.isci.2020.100951
复制
发表时间：
2020-03-27
期刊：
影响因子：
5.8
通讯作者：
Spanagel, Rainer
中科院分区：
文献类型：
--
作者：
Bilbao, Ainhoa;Neuhofer, Daniela;Spanagel, Rainer
丘脑核（NAc）在药物相关行为和自然奖赏学习中起着关键作用。多巴胺D1和D2受体介质多刺神经元（MSN）的NAc和内源性大麻素（eCB）系统中的突触可塑性已被牵连在奖励寻求。然而，奖赏寻求行为的精确分子和生理基础仍然未知。我们发现，在表达D1的MSN（D1（miR）m-GluR 5小鼠）中特异性缺失代谢型谷氨酸受体5（mGluR 5）可以消除eCB介导的长期抑郁（LTD），并阻止药物（可卡因和乙醇），自然奖励（糖精）和脑刺激寻求行为的表达。NAc核心内2-花生四烯酸甘油（2-AG）eCB信号转导的体内增强恢复了D1-（miR）mGluR 5小鼠的eCB-LTD和奖赏寻求行为。这些数据表明，一个模型中的eCB和nac的amatergic系统的一致行动，以调解奖励寻求的反应。
The nucleus accumbens (NAc) plays a key role in drug-related behavior and natural reward learning. Synaptic plasticity in dopamine D1 and D2 receptor medium spiny neurons (MSNs) of the NAc and the endogenous cannabinoid (eCB) system have been implicated in reward seeking. However, the precise molecular and physiological basis of reward-seeking behavior remains unknown. We found that the specific deletion of metabotropic glutamate receptor 5 (mGluR5) in D1-expressing MSNs (D1(miR)m-GluR5 mice) abolishes eCB-mediated long-term depression (LTD) and prevents the expression of drug (cocaine and ethanol), natural reward (saccharin), and brain-stimulation-seeking behavior. In vivo enhancement of 2-arachidonoylglycerol (2-AG) eCB signaling within the NAc core restores both eCB-LTD and reward-seeking behavior in D1-(miR)mGluR5 mice. The data suggest a model where the eCB and glutamatergic systems of the NAc act in concert to mediate reward-seeking responses.