A comparison between chlordiazepoxide and CL 218,872, a synthetic non-benzodiazepine ligand for benzodiazepine receptors, on serotonin and catecholamine turnover in brain.

Serotonin (5-HT) and catecholamine (CA) turnover rates in midbrain-hindbrain were investigated in rats treated with the benzodiazepine chlordiazepoxide (CDP) or with the anxiolytic triazolopyridazine CL 218,872. A single injection of CDP (2.5-20 mg/kg) decreased 5-HT but not CA turnover rates. Seven daily CDP injections decreased the turnover rates of both 5-HT and CA. In contrast, neither acute nor chronic administration of CL 218,872 (2.5-20 mg/kg) altered baseline turnover rates of 5-HT or CA. Since CL 218,872 has a selective affinity for Type I benzodiazepine receptors, these results suggest that stimulation of Type I receptors is not sufficient to decrease 5-HT or CA turnover rates in midbrain-hindbrain. More importantly, these results question the long-held belief that benzodiazepines exert their anxiolytic and depressant effects through reductions in 5-HT and CA turnover respectively.