Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference.
Cannabinoid type 2 receptors in dopamine neurons inhibits psychomotor behaviors, alters anxiety, depression and alcohol preference.
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DOI：
10.1038/s41598-017-17796-y
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发表时间：
2017-12-12
影响因子：
4.6
通讯作者：
Onaivi ES
中科院分区：
文献类型：
--
作者：
Liu QR;Canseco-Alba A;Zhang HY;Tagliaferro P;Chung M;Dennis E;Sanabria B;Schanz N;Escosteguy-Neto JC;Ishiguro H;Lin Z;Sgro S;Leonard CM;Santos-Junior JG;Gardner EL;Egan JM;Lee JW;Xi ZX;Onaivi ES
大麻素CB 2受体（CB 2 Rs）在小鼠脑多巴胺（DA）神经元中表达，并参与几种DA相关疾病。然而，由于CB 2 R基因敲除小鼠是组成型基因敲除，因此细胞类型特异性机制尚不清楚。因此，我们产生了与DAT-Cre小鼠杂交的Cnr 2-floxed小鼠，其中Cre-重组酶表达在多巴胺转运蛋白基因（DAT）启动子控制下，以消除DAT-Cnr 2条件性敲除（cKO）小鼠中脑DA神经元中的Cnr 2基因。利用一种新的灵敏的RNAscope原位杂交技术，我们检测到野生型和DAT-Cnr 2 cKO杂合子小鼠腹侧被盖区DA神经元中CB 2 R mRNA的表达，但在纯合子DAT-Cnr 2 cKO小鼠中没有。在这里，我们报告说，多巴胺神经元中CB 2 Rs的缺失增强了运动活动，调节了焦虑和抑郁样行为，并降低了酒精的奖励特性。我们的数据表明，CB 2 Rs参与大麻素诱导的四分体测定，大麻素与CB 1 R激动相关。GWAS的研究表明，CNR 2基因与帕金森病和物质使用障碍有关。这些结果表明，多巴胺能神经元中的CB 2 Rs可能在精神行为、焦虑、抑郁和疼痛感觉的调节以及酒精和可卡因的奖赏效应中发挥重要作用。
Cannabinoid CB2 receptors (CB2Rs) are expressed in mouse brain dopamine (DA) neurons and are involved in several DA-related disorders. However, the cell type-specific mechanisms are unclear since the CB2R gene knockout mice are constitutive gene knockout. Therefore, we generated Cnr2-floxed mice that were crossed with DAT-Cre mice, in which Cre- recombinase expression is under dopamine transporter gene (DAT) promoter control to ablate Cnr2 gene in midbrain DA neurons of DAT-Cnr2 conditional knockout (cKO) mice. Using a novel sensitive RNAscope in situ hybridization, we detected CB2R mRNA expression in VTA DA neurons in wildtype and DAT-Cnr2 cKO heterozygous but not in the homozygous DAT-Cnr2 cKO mice. Here we report that the deletion of CB2Rs in dopamine neurons enhances motor activities, modulates anxiety and depression-like behaviors and reduces the rewarding properties of alcohol. Our data reveals that CB2Rs are involved in the tetrad assay induced by cannabinoids which had been associated with CB1R agonism. GWAS studies indicates that the CNR2 gene is associated with Parkinson’s disease and substance use disorders. These results suggest that CB2Rs in dopaminergic neurons may play important roles in the modulation of psychomotor behaviors, anxiety, depression, and pain sensation and in the rewarding effects of alcohol and cocaine.
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影响因子：
3.5
作者：
Blanco-Calvo E;Rivera P;Arrabal S;Vargas A;Pavón FJ;Serrano A;Castilla-Ortega E;Galeano P;Rubio L;Suárez J;Rodriguez de Fonseca F
通讯作者：
Rodriguez de Fonseca F
影响因子：
25
作者：
Maia, Tiago V.;Frank, Michael J.
通讯作者：
Frank, Michael J.
影响因子：
5.3
作者：
Kendall DA;Yudowski GA
通讯作者：
Yudowski GA
DOI：
10.1196/annals.1432.037
发表时间：
2008-01-01
期刊：
DRUG ADDICTION: RESEARCH FRONTIERS AND TREATMENT ADVANCES
影响因子：
--
作者：
Brusco, A.;Tagliaferro, P. A.;Onaivi, E. S.
通讯作者：
Onaivi, E. S.
影响因子：
4.7
作者：
Liu, Qing-Rong;Rubio, Francisco J.;Hope, Bruce T.
通讯作者：
Hope, Bruce T.