Open AccessPsychopharmacological 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
Author(s) -
Duarte Filipe Silveira,
Duzzioni Marcelo,
Prim Rafael Luiz,
Cardozo Alcíbia Maia,
Santos Claudia Regina,
Silva Maria Goretti,
Shiozawa Maria Beatriz Cacese,
Mendes Beatriz Garcia,
Tizziani Tiago,
Brighente Inês Maria Costa,
Pizzolatti Moacir Geraldo,
Lima Thereza Christina Monteiro
Publication year - 2018
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12960
Subject(s) - anxiolytic , anticonvulsant , anxiogenic , diazepam , elevated plus maze , pharmacology , discontinuation , toxicity , withdrawal syndrome , chemistry , anxiety , medicine , anesthesia , epilepsy , psychiatry
Objectives 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. Methods 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 . Key findings 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. Conclusions 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.