Expression of functional cannabinoid CB(2) receptor in VTA dopamine neurons in rats.
Expression of functional cannabinoid CB(2) receptor in VTA dopamine neurons in rats.
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大鼠 VTA 多巴胺神经元中功能性大麻素 CB2 受体的表达。
DOI：
10.1111/adb.12367
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发表时间：
2017-05
影响因子：
3.4
通讯作者：
Xi ZX
中科院分区：
文献类型：
--
作者：
Zhang HY;Gao M;Shen H;Bi GH;Yang HJ;Liu QR;Wu J;Gardner EL;Bonci A;Xi ZX
我们最近报道了小鼠中脑多巴胺（DA）神经元中功能性大麻素CB2受体（CB2Rs）的表达。然而，由于发现CB2受体结构和表达存在显著的物种差异，因此CB2Rs在大鼠脑中的表达是否相似尚不清楚。原位杂交和免疫组化检测了可卡因自我给药大鼠腹侧被盖区（VTA） DA神经元中CB2基因和受体的表达上调。电生理研究表明，JWH133激活CB2Rs可抑制单个游离神经元的VTA DA神经元放电。全身给药JWH133没有改变，而伏隔核局部给药JWH133抑制可卡因增强的细胞外DA和静脉内可卡因自我给药。这种作用被AM630阻断，AM630是一种选择性CB2受体拮抗剂。这些数据表明CB2Rs在VTA DA神经元中表达，并在功能上调节DA神经元的活动和可卡因自我给药行为。
We have recently reported the expression of functional cannabinoid CB2 receptors (CB2Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB2Rs are similarly expressed in rat brain since significant species differences in CB2 receptor structures and expression are found. In situ hybridization and immunohistochemical assays detected CB2 gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self-administration rats. Electrophysiological studies demonstrated that activation of CB2Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and intravenous cocaine self-administration. This effect was blocked by AM630, a selective CB2 receptor antagonist. These data suggest that CB2Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats.