Braida Daniela, Limonta Valeria, Pegorini Simona, Zani Alessia, Guerini-Rocco Chiara, Gori Enzo, Sala Mariaelvina
Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy.
Psychopharmacology (Berl). 2007 Mar;190(4):441-8. doi: 10.1007/s00213-006-0639-1. Epub 2007 Jan 12.
The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals.
The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied.
Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1-10 microg/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 microg/kg) or vehicle and evaluated in a two-compartment chamber.
Salvinorin A (0.1 and 0.2 microg/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a "trance-like" effect, at doses as 5 and 10 microg/kg, was obtained. Pretreatment with the kappa-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB(1)) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 microg/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 microg/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 microg/kg produced no effect, whereas a dose of 80 microg/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 microg/kg).
Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both kappa-opioid and cannabinoid CB(1) receptors.
鼠尾草（Salvia divinorum）的主要成分Salvinorin A的幻觉效应和潜在滥用情况在动物中尚未有记录。
通过斑马鱼（Danio rerio）模型的游泳行为和条件性位置偏爱（CPP）任务，研究Salvinorin A的作用。
在肌肉注射Salvinorin A（0.1 - 10微克/千克）后，于方形观察室中测定游泳活动。对于CPP试验，给斑马鱼注射Salvinorin A（0.2和1微克/千克）或溶剂，并在两室试验箱中进行评估。
与溶剂相比，Salvinorin A（0.1和0.2微克/千克）诱导游泳行为加速，而在5和10微克/千克剂量时出现“类恍惚”效应。用κ-阿片受体拮抗剂nor - binaltorphimine（nor - BNI；10毫克/千克）和1型大麻素（CB(1)）受体拮抗剂利莫那班（1毫克/千克）预处理，分别阻断了Salvinorin A在0.2和10微克/千克剂量时产生的刺激和抑制作用。在CPP试验中，Salvinorin A（0.2和0.5微克/千克）使在与药物相关隔室中停留的时间增加。1微克/千克剂量无作用，而80微克/千克剂量诱导厌恶。用nor - BNI或利莫那班预处理完全逆转了Salvinorin A（0.5微克/千克）的强化特性。
综上所述，这些结果表明，Salvinorin A如在人类中有时所报道的那样，表现出奖赏效应，与其运动活性无关，这表明斑马鱼模型对于研究成瘾行为有用。这些效应似乎是由κ-阿片受体和大麻素CB(1)受体的激活介导的。
