The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.
The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice.
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DOI：
10.1007/s00213-014-3658-3
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发表时间：
2015-01
影响因子：
3.4
通讯作者：
Gatch, Michael B.
中科院分区：
文献类型：
--
作者：
Carbonaro, Theresa M.;Eshleman, Amy J.;Forster, Michael J.;Cheng, Kejun;Rice, Kenner C.;Gatch, Michael B.
关键词：
5-羟色胺5-HT 2A和5-HT 2C受体被认为是阿糖胞苷介导的致幻药物的主要药理学机制，但最近人们对代谢型谷氨酸（mGluR 2）受体作为致幻剂机制的贡献者产生了兴趣。本研究评估了这些5-HT和谷氨酸受体作为两种色胺致幻剂，N，N-二甲基色胺（DMT）和N，N-二异丙基色胺（DiPT）的分子靶点的作用。使用药物辨别、头部抽动和放射性配体结合测定。测试了5-HT 2AR反向激动剂（MDL 100907）、5-HT 2CR拮抗剂（SB 242084）和mGluR 2/3激动剂（LY 379268）减弱DMT和DiPT的辨别性刺激效应的能力;测试了mGluR 2/3拮抗剂（LY 341495）的增强作用。MDL 100907用于减弱由DMT和DiPT诱导的头部抽搐。在DiPT的5-HT 2CR下进行放射性配体结合研究和肌醇-1-磷酸（IP-1）蓄积。MDL 100907完全阻断DMT的辨别刺激效应，但仅部分阻断DiPT。SB 242084部分减弱了DiPT的辨别刺激效应，但对DMT的效应产生最小的衰减。LY 379268产生有效的，但只有部分阻断的区别刺激效应的DMT。LY 341495促进DMT和DiPT样效应。两种化合物均引起头部抽搐（DiPT>DMT），其被MDL 1000907阻断。DiPT在体外是5-HT 2CR的低效力完全激动剂。5-HT 2AR可能在介导两种化合物的作用中起主要作用。5-HT 2C和mGluR 2受体可能在一定程度上调节两种化合物的辨别刺激作用。
Serotonin 5-HT2A and 5-HT2C receptors are thought to be the primary pharmacological mechanisms for serotonin-mediated hallucinogenic drugs, but recently there has been interest in metabotropic glutamate (mGluR2) receptors as contributors to the mechanism of hallucinogens. The present study assesses the role of these 5-HT and glutamate receptors as molecular targets for two tryptamine hallucinogens, N,N-dimethyltryptamine (DMT) and N,N-diisopropyltryptamine (DiPT). Drug discrimination, head twitch and radioligand binding assays were used. A 5-HT2AR inverse agonist (MDL100907), 5-HT2CR antagonist (SB242084) and mGluR2/3 agonist (LY379268) were tested for their ability to attenuate the discriminative stimulus effects of DMT and DiPT; an mGluR2/3 antagonist (LY341495) was tested for potentiation. MDL100907 was used to attenuate head twitches induced by DMT and DiPT. Radioligand binding studies and inosital-1-phosphate (IP-1) accumulation were performed at the 5-HT2CR for DiPT. MDL100907 fully blocked the discriminative stimulus effects of DMT, but only partially blocked DiPT. SB242084 partially attenuated the discriminative stimulus effects of DiPT, but produced minimal attenuation of DMT’s effects. LY379268 produced potent, but only partial blockade of the discriminative stimulus effects of DMT. LY341495 facilitated DMT- and DiPT-like effects. Both compounds elicited head twitches (DiPT>DMT) which were blocked by MDL1000907. DiPT was a low potency full agonist at 5-HT2CR in vitro. The 5-HT2AR likely plays a major role in mediating the effects of both compounds. 5-HT2C and mGluR2 receptors likely modulate the discriminative stimulus effects of both compounds to some degree.
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影响因子：
16.2
作者：
OHISHI, H;OGAWAMEGURO, R;MIZUNO, N
通讯作者：
MIZUNO, N
影响因子：
3.6
作者：
Appel, JB;West, WB;Pechersky, K
通讯作者：
Pechersky, K
影响因子：
3.6
作者：
Smith, RL;Canton, H;Sanders-Bush, E
通讯作者：
Sanders-Bush, E
影响因子：
2.5
作者：
Moreno JL;Holloway T;Albizu L;Sealfon SC;González-Maeso J
通讯作者：
González-Maeso J
影响因子：
3.6
作者：
Fantegrossi, WE;Harrington, AW;Woods, JH
通讯作者：
Woods, JH