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 41 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.

中文翻译：

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致幻剂在小鼠头部抽搐反应试验中的效力与其在其他物种中的行为和主观影响之间的相关性。

5-羟色胺能致幻剂如麦角酸二乙胺 (LSD) 通过 5-HT2A 受体激活诱导啮齿动物头部抽搐。本研究的目的是确定致幻剂在小鼠头部抽搐反应 (HTR) 范式中的效力与其在其他物种（特别是大鼠和人类）中报告的效力之间是否存在相关性。在 C57BL/6J 小鼠中使用苯烷基胺和色胺致幻剂进行剂量反应实验，将可用的 HTR 效力数据库扩大到 41 种总化合物。对于可获得人类数据的药物 (n = 36)，在小鼠中的 HTR 效力与报告的人类致幻效力之间发现了强正相关 (r = 0.9448)。还发现 HTR 效力与用 LSD (r = 0.9484, n = 16) 或 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21) 训练的大鼠的替代药物鉴别 ED50 值相关. 所有这三种行为效应（小鼠的 HTR、大鼠的致幻剂辨别刺激效应和人类的迷幻效应）都与 5-HT2A 受体激活有关。我们提供的证据表明，致幻剂以非常一致的效力诱导这三种效应。除了具有高结构效度外，HTR 测定似乎还显示出显着的预测效度，证实了其在预测人类致幻剂主观效力方面的转化相关性。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和致幻剂的构效关系研究。未来对更多测试试剂的研究将评估 HTR 测定是否可用于预测 5-HT2A 激动剂在人类中的致幻效力。