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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.

Authors :
Duarte FS
Duzzioni M
Prim RL
Cardozo AM
Dos Santos CR
da Silva MG
Shiozawa MBC
Mendes BG
Tizziani T
Brighente IMC
Pizzolatti MG
de Lima TCM
Source :
The Journal of pharmacy and pharmacology [J Pharm Pharmacol] 2018 Sep; Vol. 70 (9), pp. 1272-1286. Date of Electronic Publication: 2018 Jun 28.
Publication Year :
2018

Abstract

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.<br />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.<br />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.<br />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.<br /> (© 2018 The Authors. Journal of Pharmacy and Pharmacology published by John Wiley & Sons Ltd on behalf of Royal Pharmaceutical Society.)

Details

Language :
English
ISSN :
2042-7158
Volume :
70
Issue :
9
Database :
MEDLINE
Journal :
The Journal of pharmacy and pharmacology
Publication Type :
Academic Journal
Accession number :
29956326
Full Text :
https://doi.org/10.1111/jphp.12960