Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species.
Correlation between the potency of hallucinogens in the mouse head-twitch response assay and their behavioral and subjective effects in other species.
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DOI：
10.1016/j.neuropharm.2019.107933
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发表时间：
2020-05-01
影响因子：
4.7
通讯作者：
Brandt, Simon D.
中科院分区：
文献类型：
--
作者：
Halberstadt, Adam L.;Chatha, Muhammad;Klein, Adam K.;Wallach, Jason;Brandt, Simon D.
5-羟色胺能致幻剂如麦角酸二乙胺(LSD)通过激活5-HT2A受体诱导啮齿类动物头部抽动。本研究的目的是确定迷幻剂在小鼠头部抽动反应(HTR)范式中的效力与它们在其他物种，特别是大鼠和人类中的报道效力之间是否存在相关性。在C57BL/6J小鼠体内进行了苯烷胺和色胺致幻剂的剂量-反应实验，使可用的HTR效力数据池扩大到40种化合物。对于可获得人类数据的药物(n=36)，在小鼠的htr效力和报告的人类致幻效力之间发现了强烈的正相关(r=0.9448)。研究还发现，HTR效力与服用LSD(r=0.9484，n=16)或2，5-二甲氧基-4-甲基苯丙胺(r=0.9564，n=21)训练的大鼠的替代药物辨别ED50值相关。所有这三种行为效应(小鼠的HTR，大鼠的迷幻剂识别刺激效应，以及人类的迷幻效应)都与5-HT2A受体的激活有关。我们提出的证据表明，迷幻剂以非常一致的效力诱导这三种效应。除了具有很高的结构效度外，HTR分析似乎还显示出显著的预测有效性，证实了其在预测人类致幻剂主观效力方面的翻译相关性。这些发现支持使用HTR范式作为致幻剂精神药理学的临床前模型，并用于致幻剂的结构-活性关系研究。未来对更多测试试剂的研究将评估HTR试验是否可以用于预测5-HT2A激动剂在人类身上的致幻效力。
Serotonergic hallucinogens such as lysergic acid diethylamide (LSD) induce head twitches in rodents via 5-HT2A receptor activation. The goal of the present investigation was to determine whether a correlation exists between the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm and their reported potencies in other species, specifically rats and humans. Dose-response experiments were conducted with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice, enlarging the available pool of HTR potency data to 40 total compounds. For agents where human data are available (n = 36), a strong positive correlation (r = 0.9448) was found between HTR potencies in mice and reported hallucinogenic potencies in humans. HTR potencies were also found to be correlated with published drug discrimination ED50 values for substitution in rats trained with either LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). All three of these behavioral effects (HTR in mice, hallucinogen discriminative stimulus effects in rats, and psychedelic effects in humans) have been linked to 5-HT2A receptor activation. We present evidence that hallucinogens induce these three effects with remarkably consistent potencies. In addition to having high construct validity, the HTR assay also appears to show significant predictive validity, confirming its translational relevance for predicting subjective potency of hallucinogens in humans. These findings support the use of the HTR paradigm as a preclinical model of hallucinogen psychopharmacology and in structure-activity relationship studies of hallucinogens. Future investigations with a larger number of test agents will evaluate whether the HTR assay can be used to predict the hallucinogenic potency of 5-HT2A agonists in humans.
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影响因子：
2.9
作者：
Brandt, Simon D.;Kavanagh, Pierce V.;Halberstadt, Adam L.
通讯作者：
Halberstadt, Adam L.
影响因子：
3.4
作者：
Carbonaro, Theresa M.;Eshleman, Amy J.;Forster, Michael J.;Cheng, Kejun;Rice, Kenner C.;Gatch, Michael B.
通讯作者：
Gatch, Michael B.
DOI：
10.1111/j.1476-5381.1963.tb01302.x
发表时间：
1963-01-01
期刊：
BRITISH JOURNAL OF PHARMACOLOGY AND CHEMOTHERAPY
影响因子：
--
作者：
CORNE, SJ;WARNER, BT;PICKERING, RW
通讯作者：
PICKERING, RW
影响因子：
8.2
作者：
APPEL, JB;WHITE, FJ;HOLOHEAN, AM
通讯作者：
HOLOHEAN, AM
影响因子：
7.3
作者：
Blair, JB;Kurrasch-Orbaugh, D;Nichols, DE
通讯作者：
Nichols, DE