Heteromers of ae opioid and dopamine D1 receptorsmodulate opioid-induced locomotor sensitization in a dopamine-independent manner

doi:10.1111/bph.13908

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	Heteromers of ae opioid and dopamine D1 receptorsmodulate opioid-induced locomotor sensitization in a dopamine-independent manner
	Tao, Yi-Min 2; Yu, Chuan 2; Wang, Wei-Sheng 2; Hou, Yuan-Yuan 2; Xu, Xue-Jun 2; Chi, Zhi-Qiang2 ; Ding, Yu-Qiang 1; Wang, Yu-Jun2 ; Liu, Jing-Gen2
刊名	BRITISH JOURNAL OF PHARMACOLOGY
	2017-09
卷号	174 期号:17 页码:2842-2861
ISSN号	0007-1188
DOI	10.1111/bph.13908
文献子类	Article
英文摘要	BACKGROUND AND PURPOSE Exposure to opiates induces locomotor sensitization in rodents, which has been proposed to correspond to the compulsive drug-seeking behaviour. Numerous studies have demonstrated that locomotor sensitization can occur in a dopamine transmission-independent manner; however, the underlying mechanisms are unclear. EXPERIMENTAL APPROACH Co-immunoprecipitation, BRET and cross-antagonism assays were used to demonstrate the existence of receptor heterodimers. Function of heterodimers was evaluated by behavioural studies of locomotor sensitization. KEY RESULTS The dopamine D1 receptor antagonist SCH23390 antagonized the signalling initiated by stimulation of mu opioid receptors with agonists in transfected cells expressing two receptors and in striatal tissues from wild-type but not D1 receptor knockout (KO) mice, suggesting that SCH23390 modified mu receptor function via receptor heteromers, as the ability of an antagonist of one of the receptors to inhibit signals originated by stimulation of the partner receptor was a characteristic of receptor heteromers. The existence of mu receptor-D1 receptor heterodimers was further supported by biochemical and biophysical assays. In vivo, when dopamine release was absent (by destruction of the dopaminergic projection from the ventral tegmental area to the striatum), SCH23390 still significantly inhibited mu receptor agonist-induced behavioural responses in rats. Additionally, we demonstrated that D1 or mu receptor KO mice and thus unable to form mu receptor-D1 receptor heterodimers, failed to show locomotor sensitization to morphine. CONCLUSION AND IMPLICATIONS Our results suggest that mu receptor-D1 receptor heterodimers may be involved in the dopamine-independent expression of locomotor sensitization to opiates.
资助项目	Ministry of Science and Technology of China[2013CB835100] ; Ministry of Science and Technology of China[2015CB553502] ; National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[91232716] ; National Natural Science Foundation of China[81401107] ; Committee of Science and Technology of Shanghai[13JC140680] ; Youth Innovation Promotion Association CAS[00000000]
WOS关键词	VENTRAL TEGMENTAL AREA ; SIGNAL-REGULATED KINASE ; NUCLEUS-ACCUMBENS ; BEHAVIORAL SENSITIZATION ; C-FOS ; INDUCED HYPERMOTILITY ; INVIVO MICRODIALYSIS ; MESOLIMBIC SYSTEM ; RECEPTOR AGONIST ; LIVING CELLS
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	WILEY
WOS记录号	WOS:000407420700005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272516]
专题	药理学第二研究室药物安全性评价中心
通讯作者	Wang, Yu-Jun; Liu, Jing-Gen
作者单位	1.Tongji Univ, Sch Med, Dept Anat & Neurobiol, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Tao, Yi-Min,Yu, Chuan,Wang, Wei-Sheng,et al. Heteromers of ae opioid and dopamine D1 receptorsmodulate opioid-induced locomotor sensitization in a dopamine-independent manner[J]. BRITISH JOURNAL OF PHARMACOLOGY,2017,174(17):2842-2861.
APA	Tao, Yi-Min.,Yu, Chuan.,Wang, Wei-Sheng.,Hou, Yuan-Yuan.,Xu, Xue-Jun.,...&Liu, Jing-Gen.(2017).Heteromers of ae opioid and dopamine D1 receptorsmodulate opioid-induced locomotor sensitization in a dopamine-independent manner.BRITISH JOURNAL OF PHARMACOLOGY,174(17),2842-2861.
MLA	Tao, Yi-Min,et al."Heteromers of ae opioid and dopamine D1 receptorsmodulate opioid-induced locomotor sensitization in a dopamine-independent manner".BRITISH JOURNAL OF PHARMACOLOGY 174.17(2017):2842-2861.