Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists.
Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists.
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DOI：
10.1016/j.neulet.2011.01.046
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发表时间：
2011-04-15
影响因子：
2.5
通讯作者：
González-Maeso J
中科院分区：
文献类型：
--
作者：
Moreno JL;Holloway T;Albizu L;Sealfon SC;González-Maeso J
致幻药物，包括美斯卡林、裸盖菇素和麦角酰二乙胺（LSD），作用于5-羟色胺5-HT 2A受体（5-HT 2AR）。代谢型谷氨酸受体2/3（mGluR 2/3）配体在调节由5-HT 2AR活化诱导的应答中显示出功效。5-HT 2AR-mGluR 2复合物的形成表明了影响致幻剂调节的细胞信号传导途径的功能性相互作用。在这里，我们测试了致幻性5-HT 2AR激动剂在mGluR 2敲除（mGluR 2-KO）小鼠中的细胞和行为效应。小鼠腹腔注射致幻剂DOI（2 mg/kg）和LSD（0.24 mg/kg）或溶剂。在野生型和mGluR 2-KO小鼠中测定头部抽搐行为反应、由所有5-HT 2AR激动剂诱导的c-fos表达和致幻剂特异性的fos-2表达。在小鼠额叶皮质膜制备物中通过DOI绘制[3 H]酮色林结合位移曲线。在mGluR 2-KO小鼠中消除了头部抽搐行为。在mGluR 2-KO小鼠中未检测到DOI的高亲和力结合位点。致幻剂DOI在野生型和mGluR 2-KO小鼠中诱导c-fos。然而，在mGlu 2-KO小鼠中消除了DOI对IFN-2的诱导。提示5-HT_2AR-mGluR_2复合物在致幻剂引起的神经心理反应中是必需的。
Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [3H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens.
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影响因子：
64.8
作者：
Jordan, BA;Devi, LA
通讯作者：
Devi, LA
影响因子：
4.8
作者：
Armstrong, D;Strange, PG
通讯作者：
Strange, PG
影响因子：
5
作者：
González-Maeso, J;Rodríguez-Puertas, R;Meana, JJ
通讯作者：
Meana, JJ
影响因子：
3.6
作者：
Perez, DM
通讯作者：
Perez, DM
影响因子：
64.8
作者：
Gonzalez-Maeso, Javier;Ang, Rosalind L.;Sealfon, Stuart C.
通讯作者：
Sealfon, Stuart C.