Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor.
Behavioral effects of α,α,β,β-tetradeutero-5-MeO-DMT in rats: comparison with 5-MeO-DMT administered in combination with a monoamine oxidase inhibitor.
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DOI：
10.1007/s00213-011-2616-6
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发表时间：
2012-06
影响因子：
3.4
通讯作者：
Geyer, Mark A.
中科院分区：
文献类型：
--
作者：
Halberstadt, Adam L.;Nichols, David E.;Geyer, Mark A.
关键词：
Ayahuasca是一种精神活性茶，由含有致幻色胺和单胺氧化酶抑制剂（MAOI）的植物组合制成。行为模式监测器（BPM）实验表明，5-甲氧基-N，N-二甲基色胺（5-MeO-DMT）和行为非活性剂量的MAOA抑制剂（如哈洛宁或氯吉兰）的组合诱导对大鼠运动活性的双相效应，最初减少运动，然后随着时间的推移增加活性。本研究调查了由5-MeO-DMT和MAOI的组合诱导的双相运动曲线是否是5-MeO-DMT代谢速率降低的结果。使用5-MeO-DMT的氘代衍生物（α，α，β，β-四氘代-5-MeO-DMT）对该假设进行了测试，该衍生物对MAO代谢具有抗性。证实了我们先前的发现，1.0 mg/kg 5-MeO-DMT（s.c.）对用行为失活剂量的非选择性MAOI帕吉林（10 mg/kg）预处理的大鼠的自发活动具有双相作用。单独给予5-MeO-DMT，即使剂量大于1.0 mg/kg，也仅导致自发活动减少。虽然低剂量的α，α，β，β-四氘代-5-MeO-DMT（0.3和1.0 mg/kg，s.c.）仅在BPM中产生活动减退，3.0 mg/kg的剂量诱导了与5-MeO-DMT和MAOI组合产生的类似的双相运动特征。受体结合研究表明，氘取代对5-MeO-DMT的亲和力的影响不大的各种各样的神经递质结合位点。α，α，β，β-四氘代-5-MeO-DMT的发现表明，在MAO抑制后由5-MeO-DMT诱导的活动过度是5-MeO-DMT代谢降低的结果，导致中枢5-羟色胺受体的长期占据。这些结果表明，氘代色胺可用于行为和药理学研究，以模拟色胺/MAOI组合的效果。
Ayahuasca is a psychoactive tea prepared from a combination of plants that contain a hallucinogenic tryptamine and monoamine oxidase inhibitors (MAOIs). Behavioral Pattern Monitor (BPM) experiments demonstrated that the combination of 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and a behaviorally inactive dose of an MAOA inhibitor such as harmaline or clorgyline induces biphasic effects on locomotor activity in rats, initially reducing locomotion and then increasing activity as time progresses. The present study investigated whether the biphasic locomotor profile induced by the combination of 5-MeO-DMT and an MAOI is a consequence of a reduction in the rate of 5-MeO-DMT metabolism. This hypothesis was tested using a deuterated derivative of 5-MeO-DMT (α,α,β,β-tetradeutero-5-MeO-DMT) that is resistant to metabolism by MAO. Confirming our previous findings, 1.0 mg/kg 5-MeO-DMT (s.c.) had biphasic effects on locomotor activity in rats pretreated with a behaviorally inactive dose of the nonselective MAOI pargyline (10 mg/kg). Administration of 5-MeO-DMT alone, even at doses greater than 1.0 mg/kg, produced only reductions in locomotor activity. Although low doses of α,α,β,β-tetradeutero-5-MeO-DMT (0.3 and 1.0 mg/kg, s.c.) produced only hypoactivity in the BPM, a dose of 3.0 mg/kg induced a biphasic locomotor profile similar to that produced by the combination of 5-MeO-DMT and an MAOI. Receptor binding studies demonstrated that deuterium substitution had little effect on the affinity of 5-MeO-DMT for a wide variety of neurotransmitter binding sites. The finding with α,α,β,β-tetradeutero-5-MeO-DMT indicates that the hyperactivity induced by 5-MeO-DMT after MAO inhibition is a consequence of reduced metabolism of 5-MeO-DMT, leading to prolonged occupation of central serotonin receptors. These results demonstrate that deuterated tryptamines may be useful in behavioral and pharmacological studies to mimic the effects of tryptamine/MAOI combinations.
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影响因子：
1.9
作者：
ADAMS, LM;GEYER, MA
通讯作者：
GEYER, MA
影响因子：
3.4
作者：
Halberstadt, Adam L.;Buell, Mahalah R.;Masten, Virginia L.;Risbrough, Victoria B.;Geyer, Mark A.
通讯作者：
Geyer, Mark A.
DOI：
10.1081/clt-120030949
发表时间：
2004-01-01
期刊：
JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY
影响因子：
--
作者：
Brush, DE;Bird, SB;Boyer, EW
通讯作者：
Boyer, EW
影响因子：
3.6
作者：
BEATON, JM;BARKER, SA;LIU, WF
通讯作者：
LIU, WF
影响因子：
3.6
作者：
GEYER, MA;RUSSO, PV;MASTEN, VL
通讯作者：
MASTEN, VL