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2042-71587092018SepThe Journal of pharmacy and pharmacologyJ Pharm PharmacolPsychopharmacological effects and safety of styryl-2-pyrones and dihydrostyryl-2-pyrones-rich fraction from Polygala sabulosa: absence of withdrawal syndrome and tolerance to anxiolytic-like and anticonvulsant effects.127212861272-128610.1111/jphp.12960To investigate whether mice develop tolerance to the anxiolytic-like and anticonvulsant effects of subchronic treatment with EA (the styryl-2-pyrones and dihydrostyryl-2-pyrones-rich fraction of Polygala sabulosa), as well as any withdrawal symptoms after abrupt discontinuation; to compare the effects of EA with those of diazepam (DZP) on withdrawal-induced anxiety; and to evaluate the toxicity of EA according to OECD guidelines.Male or female mice were acutely or subchronically treated with EA or DZP, and their tolerance to anxiolytic (evaluated in the elevated plus maze, EPM) and anticonvulsant effects (measured against pentylenetetrazole (PTZ)-induced convulsions) were investigated. Other groups received EA or DZP for 28 days followed by withdrawal, being the anxiety-like behaviour evaluated in the EPM.Both acute and subchronic treatments with EA induced an anxiolytic effect in the EPM. The anticonvulsant activity of DZP, but not EA, was reduced by protracted treatment. EA withdrawal retained the anxiolytic profile, while DZP withdrawal induced anxiogenesis. EA counteracted the anxiogenic-like actions of DZP withdrawal. EA has low toxicity as it did not cause any changes in the biochemical, haematological and histopathological markers.EA avoids the development of tolerance to its anxiolytic-like and anticonvulsant actions, and does not promote withdrawal syndrome. EA does not cause relevant toxic effects in rodents.© 2018 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.DuarteFilipe SilveiraFS0000-0003-0542-960XDepartment of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Pernambuco, Brazil.DuzzioniMarceloMInstitute of Biological Sciences and Health, Federal University of Alagoas, Maceió, Alagoas, Brazil.PrimRafael LuizRLDepartment of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.CardozoAlcíbia MaiaAMDepartment of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.Dos SantosClaudia ReginaCRDepartment of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.da SilvaMaria GorettiMGDepartment of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.ShiozawaMaria Beatriz CaceseMBCDepartment of Pathology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.MendesBeatriz GarciaBGDepartment of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.TizzianiTiagoTDepartment of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.BrighenteInês Maria CostaIMCDepartment of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.PizzolattiMoacir GeraldoMGDepartment of Chemistry, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.de LimaThereza Christina MonteiroTCMDepartment of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil.engJournal Article20180628
EnglandJ Pharm Pharmacol03763630022-357302-pyrone0Anti-Anxiety Agents0Anticonvulsants0Plant Extracts0PyronesIMAnimalsAnti-Anxiety Agentsisolation & purificationpharmacologyAnticonvulsantsisolation & purificationpharmacologyDrug TolerancephysiologyFemaleMaleMicePlant Extractsisolation & purificationpharmacologyPolygalaPsychopharmacologyPyronesisolation & purificationpharmacologySubstance Withdrawal SyndromePolygala sabulosaanxietyconvulsionsdihydrostyryl-2-pyronesstyryl-2-pyronestolerancewithdrawal symptomsNo conflict of interest to be declared.2018292018642018630602019110602018630602018820ppublish29956326PMC609923410.1111/jphp.12960 Bandelow B et al. Treatment of anxiety disorders. Dialogues Clin Neurosci 2017; 19: 93–107.PMC557356628867934 Farach FJ et al. Pharmacological treatment of anxiety disorders: current treatments and future directions. J Anxiety Disord 2012; 26: 833–843.PMC353972423023162Bateson AN. 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