Benzodiazepine antagonist, CGS-8216, in diazepam- or pentobarbital-dependent and non-dependent rats

CGS-8216, a benzodiazepine antagonist, was administered to rats acutely dosed with diazepam, and to rats chronically dosed with diazepam or pentobarbital. The effects of an acute dose of diazepam were antagonized by CGS-8216 but signs of precipitated abstinence were not observed. An apparent arousing effect was seen in non-dependent rats when CGS-8216 was administered after placebo, but no arousal was observed when Ro15-1788 was administered after placebo in non-dependent rats. A precipitated abstinence syndrome was elicited with CGS-8216 in rats chronically dosed with diazepam and was very similar to the abstinence syndrome precipitated by Ro15-1788 in diazepam-dependent rats. Like Ro15-1788, CGS-8216 elevated Precipitated Abstinence Scale (PAS) scores in a dose-related manner until a plateau was reached with 5 mg/kg. No signs of precipitated abstinence were observed when CGS-8216 was administered to rats dependent on phenobarbital.