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Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of

Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of

  1. NeuroChi
    Braida D, Capurro V, Zani A, Rubino T, Viganò D, Parolaro D, Sala M.
    Br J Pharmacol. 2009 Jul;157(5):844-53.

    Background and purpose: Drugs targeting brain k-opioid receptors produce profound alterations in mood. In the present
    study we investigated the possible anxiolytic- and antidepressant-like effects of the k-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. k-Opioid receptor involvement was investigated pretreating animals
    with the k-opioid receptor antagonist, nor-binaltorphimine (1 or 10 mg·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·kg-1), binding to striatal membranes of naïve rats
    and assay of fatty acid amide hydrolase in prefrontal cortex, hippocampus and amygdala.
    Key results: Salvinorin A, given s.c. (0.001–1000 mg·kg-1), exhibited both anxiolytic- and antidepressant-like effects that were
    prevented by nor-binaltorphimine or AM251 (0.5 or 3 mg·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 k-opioid
    and endocannabinoid systems and may partly explain the subjective symptoms reported by recreational users of S. divinorum.
    British Journal of Pharmacology (2009) 157, 844–853; doi:10.1111/j.1476-5381.2009.00230.x; published online 5
    May 2009