title: 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.
authors.affiliation: Netherlands Institute for Drugs and Doping Research, Department of Psychopharmacology, University of Utrecht.
authors.forename: S F
authors.initials: SF
authors.lastname: de Boer
authors.forename: J L
authors.initials: JL
authors.lastname: Slangen
authors.forename: J
authors.initials: J
authors.lastname: van der Gugten
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013312:Stress, Physiological / Q000097:blood*
chemical_list: D002395:Catecholamines; D002707:Chlordiazepoxide; D002065:Buspirone; D003345:Corticosterone