SARMAZENIL-PRECIPITATED WITHDRAWAL - A RELIABLE METHOD FOR ASSESSING DEPENDENCE LIABILITY OF BENZODIAZEPINE RECEPTOR LIGANDS

The benzodiazepine receptor partial inverse agonist sarmazenil exhibit s in vivo proconvulsive, but not convulsant, effects in different para digms in rodents. Intravenous sarmazenil challenge given at several fi xed intervals following the termination of repeated treatment with a m arkedly sedative dose of diazepam in squirrel monkeys was effective in precipitating withdrawal signs, but had no comparable effects in vehi cle-treated controls. The precipitated withdrawal reaction was not onl y robust, but it was consistently observed in all of the diazepam-trea ted monkeys. Thus, the use of sarmazenil challenge in the precipitated withdrawal paradigm provides a reliable method for assessing the deve lopment of physical dependence during repeated treatment with benzodia zepine receptor agonists. (C) 1998 Elsevier Science Inc.