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首页> 外文期刊>The European Journal of Neuroscience >Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission.
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Delta 9-tetrahydrocannabinol-induced MAPK/ERK and Elk-1 activation in vivo depends on dopaminergic transmission.

机译：体内的Delta 9-四氢大麻酚诱导的MAPK / ERK和Elk-1激活取决于多巴胺能传递。

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摘要

It is now well established that central effects of Delta 9-tetrahydrocannabinol (THC), the main psychoactive component of marijuana, are mediated by CB1 cannabinoid receptors. However, intraneuronal signalling pathways activated in vivo by THC remain poorly understood. We show that acute administration of THC induces a progressive and transient activation (i.e. phosphorylation) of the mitogen activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) in the dorsal striatum and the nucleus accumbens (NA). This activation, corresponding to both neuronal cell bodies and the surrounding neuropil, is totally inhibited by the selective antagonist of CB1 cannabinoid receptors, SR 141716A. However, blockade of dopaminergic (DA) D1 receptors by administration of SCH 23390, prior to THC, totally prevents ERK activation in the striatum, thus demonstrating a critical involvement of DA systems in THC-induced ERK activation. DA-D2 and glutamate receptors of NMDA subtypes also participate, albeit to a lesser extent, to THC-induced ERK activation in the striatum, as shown after injection of selective antagonists (raclopride and MK801, respectively). Furthermore, THC-induced phosphorylation of the transcription factor Elk-1, and up-regulation of zif268 mRNA expression are blocked by SL327, a specific inhibitor of MAPK/ERK kinase (MEK), the upstream kinase of ERK, as well as SCH 23390. Finally, using the place-preference paradigm, we show that ERK inhibition blocks THC-induced rewarding properties. Altogether, our data strongly support that ERK activation in the striatum is critically involved in long-term neuronal adaptive responses underlying THC-induced long-term behaviours.
机译：现在已经确定，大麻的主要精神活性成分Delta 9-四氢大麻酚（THC）的中心作用是由CB1大麻素受体介导的。然而，由THC在体内激活的神经内信号通路仍然知之甚少。我们显示，THC的急性给药会在背侧纹状体和伏隔核（NA）中诱导​​有丝分裂原活化的蛋白激酶/细胞外信号调节激酶（MAPK / ERK）的进行性和瞬时激活（即磷酸化）。 CB1大麻素受体SR 141716A的选择性拮抗剂完全抑制了与神经元细胞体和周围神经纤维相对应的激活。但是，在THC之前通过施用SCH 23390来阻断多巴胺能（DA）D1受体，完全可以阻止纹状体中的ERK活化，从而证明DA系统在THC诱导的ERK活化中起关键作用。注射选择性拮抗剂（分别为雷洛必利和MK801）后，NMDA亚型的DA-D2和谷氨酸受体也参与了THC诱导的纹状体中ERK活化，尽管程度较小。此外，THC诱导的转录因子Elk-1磷酸化和zif268 mRNA表达的上调被SL327（一种MAPK / ERK激酶的特异性抑制剂，ERK的上游激酶以及SCH 23390）阻止最后，使用位置偏好范式，我们显示ERK抑制作用会阻止THC诱导的奖励特性。总之，我们的数据强烈支持纹状体中的ERK激活与THC诱导的长期行为基础的长期神经元适应性反应密切相关。

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