Carbamazepine normalizes the altered behavioral and neurochemical response to stress in benzodiazepine-withdrawn rats

Rats chronically treated with diazepam (2 mg/kg per day, i.p.) for 21 days were tested 96 h after the last injection in both the forced swim test (inescapable stress) and in an active avoidance test (escapable stress). The influence of carbamazepine (7.5 mg/kg, i.p.) administered 25 min prior to each behavioral task was investigated. Withdrawn animals showed a reduced time spent in immobility in the forced swim test and an enhanced latency to escape in the active avoidance test. Both behavioral effects were normalized by a single carbamazepine administration. An additional experiment was performed to investigate the effect of a forced swim experience on cortical chloride uptake following GABA (gamma-aminobutyric acid) stimulation 96 h after diazepam withdrawal, and the influence of a single administration of carbamazepine on these effects. An increased chloride uptake was observed in vehicle-treated rats but not in diazepam-withdrawn animals following the swimming experience. Carbamazepine pretreatment enhanced chloride uptake after diazepam withdrawal but did not modify chloride flux in stressed or unstressed vehicle-treated rats. These results support the hypothesis that diazepam withdrawal affects the ability to develop adaptive responses to stress and that carbamazepine can normalize such an alteration. (C) 1997 Elsevier Science B.V.