CB2 receptors (CB2 R) are expressed in midbrain neurons. To evidence the control of dopamine release in dorsal striatum by CB2 R, we performed experiments of [3 H]-dopamine release in dorsal striatal slices. We found a paradoxical increase in K+ -induced [3 H]-dopamine release by CB2 R activation with GW 833972A and JWH 133 two selective agonist. To understand the mechanism involved, we tested for a role of the D2 autoreceptor in this effect; because in pallidal structures, the inhibitory effect of CB1 receptors (CB1 R) on GABA release is switched to a stimulatory effect by D2 receptors (D2 R). We found that the blockade of D2 autoreceptors with sulpiride prevented the stimulatory effect of CB2 R activation; in fact, under this condition, CB2 R decreased dopamine release, indicating the role of the D2 autoreceptor in the paradoxical increase. We also found that the effect occurs in nigrostriatal terminals, since lesions with 6-OH dopamine in the middle forebrain bundle prevented CB2 R effects on release. In addition, D2 -CB2 R interaction promoted cAMP accumulation, and the increase in [3 H]-dopamine release was prevented by PKA blockade. D2 -CB2 R coprecipitation and proximity ligation assay studies indicated a close interaction of receptors that could participate in the observed effects. Finally, intrastriatal injection of CB2 R agonist induced contralateral turning in amphetamine-treated rats, which was prevented by sulpiride, indicating the role of the interaction in motor behavior. Thus, these data indicate that the D2 autoreceptor switches, from inhibitory to stimulatory, the CB2 R effects on dopamine release, involving the cAMP → PKA pathway in nigrostriatal terminals.

中文翻译：

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D2 自身受体在纹状体中切换 CB2 受体对 [3 H]-多巴胺释放的影响。

CB2 受体 (CB2 R) 在中脑神经元中表达。为了证明 CB2 R 对背侧纹状体中多巴胺释放的控制，我们在背侧纹状体切片中进行了 [3 H]-多巴胺释放实验。我们发现通过使用 GW 833972A 和 JWH 133 两种选择性激动剂激活 CB2 R，K+ 诱导的 [3 H]-多巴胺释放自相矛盾地增加。为了理解所涉及的机制，我们测试了 D2 自身受体在这种效果中的作用；因为在苍白球结构中，CB1 受体 (CB1 R) 对 GABA 释放的抑制作用转换为 D2 受体 (D2 R) 的刺激作用。我们发现舒必利对 D2 自身受体的阻断阻止了 CB2 R 激活的刺激作用；事实上，在这种情况下，CB2 R 减少了多巴胺的释放，表明 D2 自身受体在反常增加中的作用。我们还发现这种影响发生在黑质纹状体末端，因为中前脑束中含有 6-OH 多巴胺的病变阻止了 CB2 R 对释放的影响。此外，D2 -CB2 R 相互作用促进了 cAMP 的积累，PKA 阻断阻止了 [3 H]-多巴胺释放的增加。D2 -CB2 R 共沉淀和邻近连接试验研究表明受体之间的密切相互作用可能参与观察到的效应。最后，纹状体内注射 CB2 R 激动剂可诱导苯丙胺治疗大鼠的对侧转向，而舒必利可防止这种情况发生，表明相互作用在运动行为中的作用。因此，这些数据表明 D2 自身受体从抑制性转变为刺激性，CB2 R 对多巴胺释放的影响，涉及黑质纹状体末端的 cAMP → PKA 通路。