Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents
Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents
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DOI：
10.1111/j.1476-5381.2009.00230.x
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发表时间：
2009-07-01
影响因子：
7.3
通讯作者：
Sala, Mariaelvina
中科院分区：
文献类型：
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作者：
Braida, Daniela;Capurro, Valeria;Sala, Mariaelvina
背景和目的：靶向脑κ-阿片受体的药物对情绪产生深刻的改变。在本研究中，我们研究了可能的抗焦虑和抗抑郁样作用的κ-阿片受体激动剂鼠尾草素A，鼠尾草的主要活性成分，在大鼠和mice.Experimental approach：实验进行了雄性Sprague-Dawley大鼠或雄性白化病瑞士小鼠。在大鼠中使用高架十字迷宫测试抗焦虑样作用。通过强迫游泳（大鼠）和悬尾（小鼠）试验评估抗抑郁样作用。研究了用κ-阿片受体拮抗剂去甲binaltorphimine预处理动物时κ-阿片受体的参与（1或10 mg中心点kg（-1）），而对CB 1大麻素受体的直接或间接活性用CB 1大麻素受体拮抗剂N-（哌啶-1-基）-5-（4-碘苯基）-1- 2，4-二氯苯基-4-甲基-1H-吡唑-3-甲酰胺（AM 251，0.5或3 mg中心点kg（-1）），与未处理大鼠的纹状体膜结合，并测定前额皮质、海马和杏仁核中的脂肪酸酰胺水解酶。鼠尾草素A，皮下给药（0.001-1000 μ g center dot kg（-1）），表现出抗焦虑和抗抑郁样作用，可被nor-binaltorphimine或AM 251（0.5或3 mg center dot kg（-1））阻止。鼠尾草素A减少杏仁核中的脂肪酸酰胺水解酶活性，但大麻素CB 1 receptor.Conclusions和影响的亲和力非常弱：抗焦虑和抗抑郁样的鼠尾草素A的作用介导的κ-阿片类和内源性大麻素系统，并可能部分解释主观症状的娱乐用户S。神圣的
Background and purpose:Drugs targeting brain kappa-opioid receptors produce profound alterations in mood. In the present study we investigated the possible anxiolytic- and antidepressant-like effects of the kappa-opioid receptor agonist salvinorin A, the main active ingredient of Salvia divinorum, in rats and mice.Experimental approach:Experiments were performed on male Sprague-Dawley rats or male Albino Swiss mice. The anxiolytic-like effects were tested by using the elevated plus maze, in rats. The antidepressant-like effect was estimated through the forced swim (rats) and the tail suspension (mice) test. kappa-Opioid receptor involvement was investigated pretreating animals with the kappa-opioid receptor antagonist, nor-binaltorphimine (1 or 10 mg center dot kg(-1)), while direct or indirect activity at CB1 cannabinoid receptors was evaluated with the CB1 cannabinoid receptor antagonist, N-(piperidin-1-yl) -5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251, 0.5 or 3 mg center dot kg(-1)), binding to striatal membranes of naive rats and assay of fatty acid amide hydrolase in prefrontal cortex, hippocampus and amygdala.Key results:Salvinorin A, given s.c. (0.001-1000 mu g center dot kg(-1)), exhibited both anxiolytic- and antidepressant-like effects that were prevented by nor-binaltorphimine or AM251 (0.5 or 3 mg center dot kg(-1)). Salvinorin A reduced fatty acid amide hydrolase activity in amygdala but had very weak affinity for cannabinoid CB1 receptors.Conclusions and implications:The anxiolytic- and antidepressant-like effects of Salvinorin A are mediated by both kappa-opioid and endocannabinoid systems and may partly explain the subjective symptoms reported by recreational users of S. divinorum.