Effects of chlordiazepoxide and buspirone on plasma catecholamine and corticosterone levels in rats under basal and stress conditions.

Abstract

The effects of the classical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-induced plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) release were investigated. Male Wistar rats provided with a permanent heart catheter and a permanent stomach catheter were used. Placement of rats into an unfamiliar cage (novel environment stress; NES), that elevated CS, NA and A, was used as a stressor. Acute administration of CDP (1-27 mg/kg) produced dose-related increases in basal plasma CS secretion but was without effect on basal NA content. The largest dose of CDP caused a slight short-term A elevation. The CDP effect on basal CS secretion tolerated with repeated drug treatment and was completely blocked after acute pretreatment with the BDZ receptor antagonist flumazenil. Acute treatment with BUSP (2-20 mg/kg) caused a marked and dose dependent increase in the plasma levels of A, NA and CS. A medium dose of CDP (9 mg/kg) attenuated the NES-induced CS and A elevations. A high dose of CDP (27 mg/kg), that elevated basal CS release, prevented a further CS increase by NES and inhibited the NA and A response to NES. BUSP (2 or 20 mg/kg) was not effective in attenuating the NES-elicited rise of CS, NA and A. However, the 20 mg/kg dose of BUSP actually enhanced the NES-induced A response. In conclusion, BUSP did not show the BDZ-like property to inhibit stress-induced elevations in CS, NA and A. Furthermore, the findings suggest that CDP and BUSP differentially affect the mechanisms controlling CS, NA and A release during basal and stress conditions.