Corticosterone increases severity of acute withdrawal from ethanol, pentobarbital, and diazepam in mice

It has been suggested that withdrawal from several subclasses of central nervous system (CNS) depressants involves common underlying mechanisms. For example, mice genetically selected for severe ethanol withdrawal convulsions (Withdrawal Seizure Prone or WSP) have also been found to express severe withdrawal following treatment with barbiturates and benzodiazepines. Corticosteroids appear to modulate severity of withdrawal from CNS depressants. Therefore, it was hypothesized that corticosterone would enhance withdrawal convulsions following acute ethanol, pentobarbital, and diazepam in WSP mice. Corticosterone (20 mg/kg) administered following each of these drugs significantly increased severity of handling-induced convulsions during withdrawal. Corticosterone did not affect pre-withdrawal convulsion scores or handling-induced convulsions of drug-naive mice. These results suggest that withdrawal convulsions following acute ethanol, pentobarbital, and diazepam are sensitive to modulation by corticosterone and they support the hypothesis that stress may increase drug withdrawal severity.