Influence of different benzodiazepines on the experimental morphine abstinence syndrome

The abuse of benzodiazepines by narcotic addicts has been well documented. However, the pharmacological basis of this abuse is not clear. In this study the effects of different benzodiazepines (flunitrazepam: 0.5, 1 and 2 mg/kg; nitrazepam: 0.5, 1, 2.5, 5 and 10 mg/kg; diazepam: 0.5, 1, 2.5, 5 and 10 mg/kg; chlordiazepoxide: 0.5, 1, 2.5, 5 and 10 mg/kg; and triazolam: 0.5, 1 and 2 mg/kg) on the morphine withdrawal syndrome in mice have been compared. Drugs were administered 30 min before naloxone-induced withdrawal. All benzodiazepines tested induced similar changes in some of the signs of morphine abstinence: decreased jumping behavior and increased wet dog shake frequency. Jumping behavior was particularly decreased by triazolam and wet dog shakes were mainly increased by flunitrazepam and nitrazepam. Forepaw treading was reduced by flunitrazepam, diazepam and triazolam, increased by nitrazepam and not changed by chlordiazepoxide. Tremor was effectively reduced by diazepam but less reliably by the other benzodiazepines. Teeth chattering was reduced by flunitrazepam and diazepam. These results indicate that benzodiazepines can interfere with the expression of the morphine withdrawal syndrome.