CARBAMAZEPINE NORMALIZES THE ALTERED BEHAVIORAL AND NEUROCHEMICAL RESPONSE TO STRESS IN BENZODIAZEPINE-WITHDRAWN RATS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 Withdrawn anim als showed a reduced time spent in immobility in the forced swim test and an enhanced latency to escape in the active avoidance test. Both b ehavioral effects were normalized by a single carbamazepine administra tion. An additional experiment was performed to investigate the effect of a forced swim experience on cortical chloride uptake following GAB A (gamma-aminobutyric acid) stimulation 96 h after diazepam withdrawal , and the influence of a single administration of carbamazepine on the se effects. An increased chloride uptake was observed in vehicle-treat ed rats but not in diazepam-withdrawn animals following the swimming e xperience. Carbamazepine pretreatment enhanced chloride uptake after d iazepam withdrawal but did not modify chloride flux in stressed or uns tressed vehicle-treated rats. These results support the hypothesis tha t diazepam withdrawal affects the ability to develop adaptive response s to stress and that carbamazepine can normalize such an alteration. ( C) 1997 Elsevier Science B.V.