A comparison between chlordiazepoxide and CL 218,872--a synthetic nonbenzodiazepine ligand for benzodiazepine receptors on spontaneous locomotor activity in rats

Abstract

Spontaneous locomotor activity was investigated in rats treated with chlordiazepoxide (CDP) or CL 218,872, a synthetic nonbenzodiazepine ligand for benzodiazepine receptors. Acute administration of CDP (2.5 mg/kg) increased activity, whereas a higher dose (10 mg/kg) decreased activity. Acute injection of CL 218,872 (2.5-10 mg/kg) produced a significant dose-dependent suppression of locomotor activity, a finding at variance with a previous report that anxiolytic doses of CL 218,872 are devoid of depressant side effects. Chronic pretreatment with CDP or CL 218,872 (10 mg/kg daily for 6 days) produced a tolerance to the sedative effect of CDP (10 mg/kg), but not to the activity suppressant action of CL 218,872 (10 mg/kg).