Butelman Eduardo R, Harris Todd J, Kreek Mary Jeanne
The Rockefeller University, 1230 York Avenue, Box 171, New York, NY 10021, USA.
Psychopharmacology (Berl). 2004 Mar;172(2):220-4. doi: 10.1007/s00213-003-1638-0. Epub 2003 Oct 30.
Salvinorin A is the active component of the hallucinogenic plant Salvia divinorum. The potential mode of action of this hallucinogen was unknown until recently. A recent in vitro study detected high affinity and efficacy of salvinorin A at kappa-opioid receptors. It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy kappa-agonist (U69,593) in rhesus monkeys.
Monkeys were previously trained to discriminate U69,593 (0.0056 or 0.013 mg/kg; s.c.) from vehicle in a food-reinforced FR20 (fixed ratio 20) operant conditioning procedure (n=3). The ability of salvinorin A to cause generalization (> or =90% U69,593-appropriate responding) was examined in time course and cumulative dose-effect curve studies.
All subjects dose-dependently emitted full U69,593-appropriate responding after salvinorin A (0.001-0.032 mg/kg, SC). Salvinorin A-induced generalization started 5-15 min after injection, and dissipated by 120 min. The opioid antagonist quadazocine (0.32 mg/kg) fully blocked the effects of salvinorin A. The kappa-selective antagonist GNTI (1 mg/kg; 24 h pretreatment) did not cause significant antagonism of the effects of salvinorin A (GNTI, under these conditions, was only effective as an antagonist in two of three monkeys). The NMDA antagonist ketamine (0.1-3.2 mg/kg) was not generalized by any subject, indicating that not all compounds that produce hallucinogenic or psychotomimetic effects in humans are generalized by subjects trained to discriminate U69,593.
The naturally occurring hallucinogen salvinorin A produces discriminative stimulus effects similar to those of a high efficacy kappa-agonist in non-human primates.
Salvinorin A是致幻植物鼠尾草的活性成分。直到最近，这种致幻剂的潜在作用方式仍不为人知。最近的一项体外研究检测到Salvinorin A对κ-阿片受体具有高亲和力和效力。据推测，Salvinorin A在恒河猴中会产生与高效κ-激动剂（U69,593）类似的辨别性刺激效应。
在一项食物强化的FR20（固定比率20）操作条件反射程序中，先前训练猴子区分U69,593（0.0056或0.013mg/kg；皮下注射）和溶剂（n = 3）。在时间进程和累积剂量-效应曲线研究中，检测Salvinorin A引起泛化（≥90%与U69,593相符的反应）的能力。
所有受试动物在注射Salvinorin A（0.001 - 0.032mg/kg，皮下注射）后，均出现剂量依赖性的完全与U69,593相符的反应。Salvinorin A诱导的泛化在注射后5 - 15分钟开始，并在120分钟内消失。阿片类拮抗剂夸达佐辛（0.32mg/kg）完全阻断了Salvinorin A的效应。κ-选择性拮抗剂GNTI（1mg/kg；预处理24小时）并未对Salvinorin A的效应产生显著拮抗作用（在这些条件下，GNTI仅在三只猴子中的两只中作为拮抗剂有效）。NMDA拮抗剂氯胺酮（0.1 - 3.2mg/kg）未被任何受试动物泛化，这表明并非所有在人类中产生致幻或拟精神病效应的化合物都会被训练区分U69,593的受试动物泛化。
天然存在的致幻剂Salvinorin A在非人灵长类动物中产生与高效κ-激动剂类似的辨别性刺激效应。
