國家衛生研究院 NHRI:Item 3990099045/9875
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/9875


    Title: Orexins contribute to restraint stress-induced cocaine relapse by endocannabinoid-mediated disinhibition of dopaminergic neurons
    Authors: Tung, LW;Lu, GL;Lee, YH;Yu, L;Lee, HJ;Leishman, E;Bradshaw, H;Hwang, LL;Hung, MS;Mackie, K;Zimmer, A;Chiou, LC
    Contributors: Institute of Biotechnology and Pharmaceutical Research
    Abstract: Orexins are associated with drug relapse in rodents. Here, we show that acute restraint stress in mice activates lateral hypothalamic (LH) orexin neurons, increases levels of orexin A and 2-arachidonoylglycerol (2-AG) in the ventral tegmental area (VTA), and reinstates extinguished cocaine-conditioned place preference (CPP). This stress-induced reinstatement of cocaine CPP depends on type 1 orexin receptors (OX1Rs), type 1 cannabinoid receptors (CB1Rs) and diacylglycerol lipase (DAGL) in the VTA. In dopaminergic neurons of VTA slices, orexin A presynaptically inhibits GABAergic transmission. This effect is prevented by internal GDP-beta-S or inhibiting OX1Rs, CB1Rs, phospholipase C or DAGL, and potentiated by inhibiting 2-AG degradation. These results suggest that restraint stress activates LH orexin neurons, releasing orexins into the VTA to activate postsynaptic OX1Rs of dopaminergic neurons and generate 2-AG through a Gq-protein-phospholipase C-DAGL cascade. 2-AG retrogradely inhibits GABA release through presynaptic CB1Rs, leading to VTA dopaminergic disinhibition and reinstatement of cocaine CPP.
    Date: 2016-07-22
    Relation: Nature Communications. 2016 Jul 22;7:Article number 12199.
    Link to: http://dx.doi.org/10.1038/ncomms12199
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000380838300001
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84979261652
    Appears in Collections:[Ming-Shiu Hung] Periodical Articles

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