@conference{
author = "Divljaković, Jovana and Timić, Tamara and Milinković, Marija M. and Batinić, Bojan and van Linn, Michael and Cook, James M. and Savić, Miroslav",
year = "2012",
abstract = "Objective : Despite a half century of clinical use and the recognized
potential of benzodiazepine dependence, the mechanisms under-
lying benzodiazepine withdrawal remain insufficiently understood.
The aim of the present study was to assess the influence of the non-
selective antagonist (flumazenil) and the preferential a1-subunit
selective antagonist (bCCt) on the anxiety level after diazepam with-
drawal.
Methods : The male Wistar rats were protractedly treated during
21 days with diazepam (2 mg/kg) or solvent. On the testing day,
24 hours after the last injection, animals from the diazepam-treated
groups received either antagonist (flumazenil or bCCt) or solvent, and
animals from the solvent-treated groups received solvent or diaze-
pam. Twenty minutes after administration of treatment on the testing
day, single animals were placed in the elevated plus maze in order to
assess the level of anxiety.
Results : Two-way ANOVA revealed that animals withdrawn from
diazepam spent significantly less time on the open arms than control
animals (p=0.023). One-way ANOVA, followed by post hoc test, re-
vealed that administration of flumazenil (10 mg/kg) or bCCt (1.25,
5 or 20 mg/kg) reversed the diazepam withdrawal-induced anxiety
(percentage of open arm time : p=0.003, p=0.032, p=0.031 and
p=0.014 compared to the diazepam-withdrawn group, respectively).
Concomitant administration of antagonists (10 mg/kg flumazenil,
or 1.25, 5 or 20 mg/kg bCCt) induced an anxiolytic effect comparable
to that observed after acutely administrated diazepam (percentage of
open arm time : p=0.142, p=0.187, p=0.243 and p=0.290, respect-
ively).
Conclusion : The present study demonstrated that administration
of the a1-selective antagonist bCCt or non-selective antagonist
flumazenil could prevent the withdrawal-induced anxiety and also
induce an anxiolytic-like effect. Moreover, presented results have
suggested that mechanism of preventing the withdrawal-induced
anxiety involves the antagonism at a1-containing GABAA receptors.",
publisher = "Oxford Univ Press, Oxford",
journal = "International Journal of Neuropsychopharmacology",
title = "Beta CCT as well as flumazenil prevent the diazepam withdrawal-induced anxiety in the elevated plus maze in rats",
volume = "15",
number = "Supplement 1",
pages = "201-201",
doi = "10.1017/S1461145712000508",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1661"
}