Carbamazepine normalizes the altered behavioral and neurochemical response to stress in benzodiazepine-withdrawn rats.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 Withdrawn animals showed a reduced time spent in immobility in the forced swim test and an enhanced latency to escape in the active avoidance test.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 An increased chloride uptake was observed in vehicle-treated rats but not in diazepam-withdrawn animals following the swimming experience.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.
Martijena
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Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Lacerra
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Molina
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D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000493:pharmacokinetics; D003975:Diazepam / Q000009:adverse effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology; D013268:Stimulation, Chemical; D013312:Stress, Physiological / Q000188:drug therapy* / Q000209:etiology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology; D013550:Swimming; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; D014151:Anti-Anxiety Agents; D002712:Chlorides; D011963:Receptors, GABA-A; D002220:Carbamazepine; D005680:gamma-Aminobutyric Acid; D003975:Diazepam