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典型文献
Repeated cocaine administration upregulates CB2 receptor expression in striatal medium-spiny neurons that express dopamine D1 receptors in mice
文献摘要:
Cannabinoid CB2 receptors(CB2R)are importantly involved in drug reward and addiction.However,the cellular mechanisms underlying CB2R action remain unclear.We have previously reported that cocaine self-administration upregulates CB2R expression in midbrain dopamine(DA)neurons.In the present study,we investigated whether cocaine or heroin also alters CB2R expression in striatal medium-spiny neurons that express dopamine D1 or D2 receptors(D,-MSNs,D2-MSNs)and microglia.Due to the concern of CB2R antibody specificity,we developed three mouse CB2-specific probes to detect CB2R mRNA using quantitative RT-PCR and RNAscope in situ hybridization(ISH)assays.We found that a single injection of cocaine failed to alter,while repeated cocaine injections or self-administration dose-dependently upregulated CB2R gene expression in both brain(cortex and striatum)and periphery(spleen).In contrast,repeated administration of heroin produced a dose-dependent reduction in striatal CB2 mRNA expression.RNAscope ISH assays detected CB2R mRNA in striatal D1-and D2-MSNs,not in microglia.We then used transgenic CX3CR1eGFP/+microglia reporter mice and D1-or D2-Cre-RiboTag mice to purify striatal microglia or ribosome-associated mRNAs from CX3CR1eGFP/+,D1-MSNs,or D2-MSNs,respectively.We found that CB2R upregulation occurred mainly in D1-MSNs,not in D2-MSNs or microglia,in the nucleus accumbens rather than the dorsal striatum.These findings indicate that repeated cocaine exposure may upregulate CB2R expression in both brain and spleen,with regional and cell type-specific profiles.In the striatum,CB2R upregulation occurs mainly in D1-MSNs in the nucleus accumbens.Given the important role of D1-MSNs in brain reward function,the present findings provide new insight into mechanisms by which brain CB2Rs modulate cocaine action.
文献关键词:
作者姓名:
Hai-Ying Zhang;Lindsay De Biase;Ramesh Chandra;Hui Shen;Qing-Rong Liu;Eliot Gardner;Mary Kay Lobo;Zheng-Xiong Xi
作者机构:
Intramural Research Program,National Institute on Drug Abuse,Baltimore,USA;Section on Molecular Neuroscience,National Institute of Mental Health,Bethesda,USA;Department of Physiology,David Geffen School of Medicine at University of California,Los Angeles,Los Angeles,CA,USA;Department of Anatomy and Neurobiology,University of Maryland School of Medicine,Baltimore,USA;Laboratory of Clinical Investigation,Intramural Research Program,National Institute on Aging,Baltimore,USA
引用格式:
[1]Hai-Ying Zhang;Lindsay De Biase;Ramesh Chandra;Hui Shen;Qing-Rong Liu;Eliot Gardner;Mary Kay Lobo;Zheng-Xiong Xi-.Repeated cocaine administration upregulates CB2 receptor expression in striatal medium-spiny neurons that express dopamine D1 receptors in mice)[J].中国药理学报(英文版),2022(04):876-888
A类:
Cannabinoid,CX3CR1eGFP,+microglia,RiboTag,CB2Rs
B类:
Repeated,cocaine,administration,upregulates,expression,striatal,medium,spiny,neurons,that,dopamine,D1,receptors,mice,are,importantly,involved,drug,reward,addiction,However,cellular,mechanisms,underlying,action,remain,unclear,We,have,previously,reported,self,midbrain,DA,In,present,study,investigated,whether,heroin,also,alters,D2,MSNs,Due,concern,antibody,specificity,developed,three,mouse,probes,using,quantitative,RNAscope,situ,hybridization,ISH,assays,found,single,failed,while,repeated,injections,dose,dependently,upregulated,gene,both,cortex,striatum,periphery,spleen,contrast,produced,reduction,detected,not,then,used,transgenic,reporter,Cre,purify,ribosome,associated,mRNAs,from,respectively,upregulation,occurred,mainly,nucleus,accumbens,rather,than,dorsal,These,findings,indicate,exposure,may,regional,type,profiles,occurs,Given,role,function,provide,new,insight,into,by,which,modulate
AB值:
0.404143
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