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- Title
Potential anxiolytic- and antidepressant-like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents.
- Authors
Braida, Daniela; Capurro, Valeria; Zani, Alessia; Rubino, Tiziana; Viganò, Daniela; Parolaro, Daniela; Sala, Mariaelvina; Viganò, Daniela
- Abstract
<bold>Background and Purpose: </bold>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.<bold>Experimental Approach: </bold>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 mgxkg(-1)), while direct or indirect activity at CB(1) cannabinoid receptors was evaluated with the CB(1) 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 mgxkg(-1)), binding to striatal membranes of naïve rats and assay of fatty acid amide hydrolase in prefrontal cortex, hippocampus and amygdala.<bold>Key Results: </bold>Salvinorin A, given s.c. (0.001-1000 microgxkg(-1)), exhibited both anxiolytic- and antidepressant-like effects that were prevented by nor-binaltorphimine or AM251 (0.5 or 3 mgxkg(-1)). Salvinorin A reduced fatty acid amide hydrolase activity in amygdala but had very weak affinity for cannabinoid CB(1) receptors.<bold>Conclusions and Implications: </bold>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.
- Subjects
OPIOID receptors; ANTIDEPRESSANTS; PREFRONTAL cortex; TARGETED drug delivery; FATTY acids; SALVIA divinorum; RODENTS; BRAIN metabolism; HYDROCARBON metabolism; CHEMICAL alcohol metabolism; SUBCUTANEOUS injections; AMIDASES; ANIMAL behavior; ANIMAL experimentation; BINDING sites; BIOLOGICAL models; BRAIN; CELL receptors; COMPARATIVE studies; DOSE-effect relationship in pharmacology; EMOTIONS; HETEROCYCLIC compounds; HYDROCARBONS; RESEARCH methodology; MEDICAL cooperation; MICE; MOTOR ability; NALTREXONE; NARCOTIC antagonists; PIPERIDINE; PLANTS; RATS; RESEARCH; SWIMMING; TRANQUILIZING drugs; EVALUATION research; PHARMACODYNAMICS
- Publication
British Journal of Pharmacology, 2009, Vol 157, Issue 5, p844
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1111/j.1476-5381.2009.00230.x