{"PubmedArticle":{"MedlineCitation":{"@attributes":{"Status":"MEDLINE","Owner":"NLM","IndexingMethod":"Manual"},"PMID":{"@attributes":{"Version":"1"},"@text":"29956326"},"DateCompleted":{"Year":"2019","Month":"01","Day":"09"},"DateRevised":{"Year":"2019","Month":"01","Day":"09"},"Article":{"@attributes":{"PubModel":"Print-Electronic"},"Journal":{"ISSN":{"@attributes":{"IssnType":"Electronic"},"@text":"2042-7158"},"JournalIssue":{"@attributes":{"CitedMedium":"Internet"},"Volume":"70","Issue":"9","PubDate":{"Year":"2018","Month":"Sep"}},"Title":"The Journal of pharmacy and pharmacology","ISOAbbreviation":"J Pharm Pharmacol"},"ArticleTitle":"Psychopharmacological 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.","Pagination":{"StartPage":"1272","EndPage":"1286","MedlinePgn":"1272-1286"},"ELocationID":[{"@attributes":{"EIdType":"doi","ValidYN":"Y"},"@text":"10.1111\/jphp.12960"}],"Abstract":{"AbstractText":[{"@attributes":{"Label":"OBJECTIVES","NlmCategory":"OBJECTIVE"},"@text":"To 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."},{"@attributes":{"Label":"METHODS","NlmCategory":"METHODS"},"@text":"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."},{"@attributes":{"Label":"KEY FINDINGS","NlmCategory":"RESULTS"},"@text":"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."},{"@attributes":{"Label":"CONCLUSIONS","NlmCategory":"CONCLUSIONS"},"@text":"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."}],"CopyrightInformation":"\u00a9 2018 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society."},"AuthorList":{"@attributes":{"CompleteYN":"Y"},"Author":[{"@attributes":{"ValidYN":"Y"},"LastName":"Duarte","ForeName":"Filipe Silveira","Initials":"FS","Identifier":[{"@attributes":{"Source":"ORCID"},"@text":"0000-0003-0542-960X"}],"AffiliationInfo":[{"Affiliation":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Pernambuco, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Duzzioni","ForeName":"Marcelo","Initials":"M","AffiliationInfo":[{"Affiliation":"Institute of Biological Sciences and Health, Federal University of Alagoas, Macei\u00f3, Alagoas, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Prim","ForeName":"Rafael Luiz","Initials":"RL","AffiliationInfo":[{"Affiliation":"Department of Pathology, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Cardozo","ForeName":"Alc\u00edbia Maia","Initials":"AM","AffiliationInfo":[{"Affiliation":"Department of Pathology, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Dos Santos","ForeName":"Claudia Regina","Initials":"CR","AffiliationInfo":[{"Affiliation":"Department of Pathology, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"da Silva","ForeName":"Maria Goretti","Initials":"MG","AffiliationInfo":[{"Affiliation":"Department of Pathology, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Shiozawa","ForeName":"Maria Beatriz Cacese","Initials":"MBC","AffiliationInfo":[{"Affiliation":"Department of Pathology, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Mendes","ForeName":"Beatriz Garcia","Initials":"BG","AffiliationInfo":[{"Affiliation":"Department of Chemistry, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Tizziani","ForeName":"Tiago","Initials":"T","AffiliationInfo":[{"Affiliation":"Department of Chemistry, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Brighente","ForeName":"In\u00eas Maria Costa","Initials":"IMC","AffiliationInfo":[{"Affiliation":"Department of Chemistry, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"Pizzolatti","ForeName":"Moacir Geraldo","Initials":"MG","AffiliationInfo":[{"Affiliation":"Department of Chemistry, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]},{"@attributes":{"ValidYN":"Y"},"LastName":"de Lima","ForeName":"Thereza Christina Monteiro","Initials":"TCM","AffiliationInfo":[{"Affiliation":"Department of Pharmacology, Federal University of Santa Catarina, Florian\u00f3polis, Santa Catarina, Brazil."}]}]},"Language":["eng"],"PublicationTypeList":{"PublicationType":[{"@attributes":{"UI":"D016428"},"@text":"Journal Article"}]},"ArticleDate":[{"@attributes":{"DateType":"Electronic"},"Year":"2018","Month":"06","Day":"28"}]},"MedlineJournalInfo":{"Country":"England","MedlineTA":"J Pharm Pharmacol","NlmUniqueID":"0376363","ISSNLinking":"0022-3573"},"ChemicalList":{"Chemical":[{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"C584017"},"@text":"2-pyrone"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D014151"},"@text":"Anti-Anxiety Agents"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D000927"},"@text":"Anticonvulsants"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D010936"},"@text":"Plant Extracts"}},{"RegistryNumber":"0","NameOfSubstance":{"@attributes":{"UI":"D011753"},"@text":"Pyrones"}}]},"CitationSubset":["IM"],"MeshHeadingList":{"MeshHeading":[{"DescriptorName":{"@attributes":{"UI":"D000818","MajorTopicYN":"N"},"@text":"Animals"}},{"DescriptorName":{"@attributes":{"UI":"D014151","MajorTopicYN":"N"},"@text":"Anti-Anxiety Agents"},"QualifierName":[{"@attributes":{"UI":"Q000302","MajorTopicYN":"N"},"@text":"isolation & purification"},{"@attributes":{"UI":"Q000494","MajorTopicYN":"Y"},"@text":"pharmacology"}]},{"DescriptorName":{"@attributes":{"UI":"D000927","MajorTopicYN":"N"},"@text":"Anticonvulsants"},"QualifierName":[{"@attributes":{"UI":"Q000302","MajorTopicYN":"N"},"@text":"isolation & 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sabulosa"},{"@attributes":{"MajorTopicYN":"N"},"@text":"anxiety"},{"@attributes":{"MajorTopicYN":"N"},"@text":"convulsions"},{"@attributes":{"MajorTopicYN":"N"},"@text":"dihydrostyryl-2-pyrones"},{"@attributes":{"MajorTopicYN":"N"},"@text":"styryl-2-pyrones"},{"@attributes":{"MajorTopicYN":"N"},"@text":"tolerance"},{"@attributes":{"MajorTopicYN":"N"},"@text":"withdrawal symptoms"}]}],"CoiStatement":"No conflict of interest to be declared."},"PubmedData":{"History":{"PubMedPubDate":[{"@attributes":{"PubStatus":"received"},"Year":"2018","Month":"2","Day":"9"},{"@attributes":{"PubStatus":"accepted"},"Year":"2018","Month":"6","Day":"4"},{"@attributes":{"PubStatus":"pubmed"},"Year":"2018","Month":"6","Day":"30","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"medline"},"Year":"2019","Month":"1","Day":"10","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"entrez"},"Year":"2018","Month":"6","Day":"30","Hour":"6","Minute":"0"},{"@attributes":{"PubStatus":"pmc-release"},"Year":"2018","Month":"8","Day":"20"}]},"PublicationStatus":"ppublish","ArticleIdList":{"ArticleId":[{"@attributes":{"IdType":"pubmed"},"@text":"29956326"},{"@attributes":{"IdType":"pmc"},"@text":"PMC6099234"},{"@attributes":{"IdType":"doi"},"@text":"10.1111\/jphp.12960"}]},"ReferenceList":[{"Reference":[{"Citation":"Bandelow B\n<i>et al.<\/i>\nTreatment of anxiety disorders. 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