Hallucinatory and rewarding effect of salvinorin A in zebrafish:: κ-opioid and CB1-cannabinoid receptor involvement
Hallucinatory and rewarding effect of salvinorin A in zebrafish:: κ-opioid and CB1-cannabinoid receptor involvement
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DOI：
10.1007/s00213-006-0639-1
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发表时间：
2007-03-01
影响因子：
3.4
通讯作者：
Sala, Mariaelvina
中科院分区：
文献类型：
--
作者：
Braida, Daniela;Limonta, Valeria;Sala, Mariaelvina
目的研究鼠尾草素A（salvinorin A）对斑马鱼（Danio rerio）游泳行为和条件性位置偏爱（conditioned place preference，CPP）的影响。鼠尾草素A处理（0.1-10 μ g/kg）。对于CPP测试，斑马鱼给予salvinorin A（0.2和1 μ g/kg）或车辆，并在一个两室chamber.Results鼠尾草素A（0.1和0.2 μ g/kg）诱导加速游泳行为与车辆相比，而“恍惚样”的效果，在剂量为5和10 μ g/kg，获得。用κ-阿片样物质拮抗剂去甲-binaltorphimine（去甲-BNI; 10 mg/kg）和大麻素1型（CB 1）拮抗剂利莫那班（1 mg/kg）预处理，分别阻断了在0.2和10 μ g/kg剂量下获得的鼠尾草素A诱导的刺激和抑制作用。在CPP试验中，鼠尾草素A（0.2和0.5 μ g/kg）使药物相关隔室中花费的时间增加。1 μ g/kg的剂量没有产生任何作用，而80 μ g/kg的剂量诱导厌恶。用去甲-BNI或利莫那班预处理完全逆转了鼠尾草素A（0.5 μ g/kg）的增强特性。总之，这些结果表明，鼠尾草素A，有时在人类中报道，表现出奖励作用，独立于其运动活性，这表明斑马鱼模型研究成瘾行为的有用性。这些作用似乎是由κ-阿片样物质和大麻素CB 1受体的激活介导的。
Rationale The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals.Objective The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied.Materials and Methods Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1-10 mu g/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 mu g/kg) or vehicle and evaluated in a two-compartment chamber.Results Salvinorin A (0.1 and 0.2 mu g/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a "trance-like" effect, at doses as 5 and 10 mu g/kg, was obtained. Pretreatment with the kappa-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB1) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 mu g/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 mu g/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 mu g/kg produced no effect, whereas a dose of 80 mu g/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 mu g/kg).Conclusions 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 CB1 receptors.