Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.
Modification of 5-methoxy-N,N-dimethyltryptamine-induced hyperactivity by monoamine oxidase A inhibitor harmaline in mice and the underlying serotonergic mechanisms.
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DOI：
10.1016/j.pharep.2016.01.008
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Yu AM
中科院分区：
文献类型：
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作者：
Jiang XL;Shen HW;Yu AM
5-甲氧基-N，N-二甲基色胺（5-MeO-DMT）和吲哚胺（IAA）是常被同时滥用的两种吲哚胺类药物。我们最近的研究表明，共同管理harlycine，单胺氧化酶抑制剂（MAOI），对5-MeO-DMT的药代动力学和体温调节的显着影响。本研究旨在探讨5-羟色胺（5-HT）受体在5-MeO-DMT对小鼠笼内活动的影响。在植入遥测发射器和给予不同剂量的IAA药物和5-HT受体拮抗剂后，在饲养笼中自动监测个体动物的饲养笼活动。采用梯形法则计算小鼠活动值的效应曲线下面积（AUEC）。高剂量肝素（15 mg/kg，ip）单独给药可引起小鼠早期（0-45 min）活动减退，5-HT 1A受体拮抗剂WAY-100635可完全抑制，而5-HT 2A受体拮抗剂MDL-100907可减轻晚期（45-180 min）活动亢进。单独5-MeO-DMT（10和20 mg/kg，ip）诱导双相效应，早期（0-45 min）活动减退（WAY-100635完全减弱）和晚期（45-180 min）活动过度（MDL-100907完全抑制）。有趣的是，MAOI干扰素（2-15 mg/kg）与阈下剂量的5-MeO-DMT（2 mg/kg）联合给药在晚期（45-180 min）诱导过度活动，可通过WAY-100635或MDL-100907消除。MAOI与5-MeO-DMT的联合给药引起过度的晚期活动过度，这涉及5-HT 1A和5-HT 2A受体的激活。
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are indolealkylamine (IAA) drugs often abused together. Our recent studies have revealed the significant effects of co-administered harmaline, a monoamine oxidase inhibitor (MAOI), on 5-MeO-DMT pharmacokinetics and thermoregulation. This study was to delineate the impact of harmaline and 5-MeO-DMT on home-cage activity in mouse models, as well as the contribution of serotonin (5-HT) receptors. Home-cage activities of individual animals were monitored automatically in the home cages following implantation of telemetry transmitters and administration of various doses of IAA drugs and 5-HT receptor antagonists. Area under the effect curve (AUEC) of mouse activity values were calculated by trapezoidal rule. High dose of harmaline (15 mg/kg, ip) alone caused an early-phase (0–45 min) hypoactivity in mice that was fully attenuated by 5-HT1A receptor antagonist WAY-100635, whereas a late-phase (45–180 min) hyperactivity that was reduced by 5-HT2A receptor antagonist MDL-100907. 5-MeO-DMT (10 and 20 mg/kg, ip) alone induced biphasic effects, an early-phase (0–45 min) hypoactivity that was completely attenuated by WAY-100635, and a late-phase (45–180 min) hyperactivity that was fully suppressed by MDL-100907. Interestingly, co-administration of MAOI harmaline (2–15 mg/kg) with a subthreshold dose of 5-MeO-DMT (2 mg/kg) induced excessive hyperactivities at late phase (45–180 min) that could be abolished by either WAY-100635 or MDL-100907. Co-administration of MAOI with 5-MeO-DMT provokes excessive late-phase hyperactivity, which involves the activation of both 5-HT1A and 5-HT2A receptors.