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Anthocyanins modify diazepam dependence in rats


Chronic use of high doses of benzodiazepines may lead to development of tolerance and dependence. Long-term administration of diazepam causes CNS changes: significantly increased amount of GABA required for neuronal activity inhibition; reduced efficacy of diazepam on GABA-evoked Cl- currents [1]; functional changes in the chloride channel related to withdrawal signs [2]; changes in glutamate receptors [3]. Our previous data showed that anthocyanins diminished diazepam toxicity and significantly enhanced the survival of mice, treated with lethal doses of diazepam. Anthocyanins are naturally occurring flavonoids with various pharmacological activities. Literature data determine flavonoids as benzodiazepine receptor ligands [4]. We estimated withdrawal signs in the experimental rats in order to evaluate the effects of anthocyanins on diazepam dependence.

Materials and methods

Wistar rats were divided into three groups: I - diazepam; II - diazepam + anthocyanins 100 mg/kg; III - diazepam + anthocyanins 200 mg/kg. Rats were treated for 60 days. We evaluated fast breathing, hypermotility, seizures, tremor and piloerection as withdrawal signs after discontinuation of diazepam.


Our results showed that the administration of anthocyanins significantly decreased abstinent signs of diazepam dependent rats. The most prominent effects were observed in the “diazepam + anthocyanins 200 mg/kg” group.


Anthocyanins administered together with diazepam are able to diminish diazepam dependence and can be used preventively in cases that require chronic therapy with benzodiazepines.


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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Drenska, D., Varadinova, M. Anthocyanins modify diazepam dependence in rats. Ann Gen Psychiatry 7 (Suppl 1), S349 (2008).

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