文章基本信息

标题：Endocannabinoid LTD in Accumbal D1 Neurons Mediates Reward-Seeking Behavior
本地全文：下载
作者：Ainhoa Bilbao ; Daniela Neuhofer ; Marja Sepers 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：3
页码：1-34
DOI：10.1016/j.isci.2020.100951
语种：English
出版社：Elsevier
摘要：SummaryThe 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 (D1miRmGluR5 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 vivoenhancement of 2-arachidonoylglycerol (2-AG) eCB signaling within the NAc core restores both eCB-LTD and reward-seeking behavior in D1miRmGluR5 mice. The data suggest a model where the eCB and glutamatergic systems of the NAc act in concert to mediate reward-seeking responses.Graphical AbstractDisplay OmittedHighlights•mGluR5-D1-CB1-induced eCB-LTD mediates drugs of abuse and natural reward seeking•eCB-LTD in D2-MSNs plays no important role in processing of reward-seeking responses•Loss of eCB-LTD is a consequence of higher MAGL activity and lower CB1R expression•Acute drug administration stops craving for alternative rewards on following daysNeuroscience; Behavioral Neuroscience; Molecular Neuroscience