title: Effects of buspirone and chlordiazepoxide on plasma catecholamine and corticosterone levels in stressed and nonstressed rats.
abstract: The effects of intragastric administration of the prototypical benzodiazepine (BDZ) anxiolytic drug chlordiazepoxide (CDP) and the non-BDZ anxiolytic agent buspirone (BUSP) on basal and stress-elevated plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) contents were investigated. Acute dosing of CDP (1-27 mg/kg) produced dose-related increases in basal CS secretion but was without effect on basal NA levels. The high dose of CDP caused a slight short-term A increase. Dose-dependent increases in plasma A, NA and CS contents were observed after acute treatment with BUSP (2 and 20 mg/kg). A medium dose of CDP (9 mg/kg) attenuated the stress-induced CS and A elevations. High doses of CDP that elevated basal CS release prevented a further increase of CS by stress and inhibited the NA and A response to stress. BUSP (2 and 20 mg/kg) was not effective in decreasing the stress-elicited rise of CS, NA or A. Conversely, the 20 mg/kg dose of BUSP enhanced the stress-induced A response. Repeated administration of CDP (9 mg/kg/day for six days) produced tolerance to the elevation of basal CS triggered by acute CDP treatment, but increased the efficacy of the drug's CS and A attenuating action in stressed rats. Repeated administration of BUSP (2 mg/kg/day for six days) also produced tolerance to the acute BUSP-induced effect on basal CS release, but did not affect the stress-induced CS, NA and A responses. It is concluded that the clinically effective anxiolytic BUSP does not have the BDZ-like property to inhibit stress-induced elevations in CS, NA and A. Furthermore, the present data support other evidence that activation of 5-HT1A receptor mechanisms increases plasma catecholamine and corticosterone concentrations.
authors.affiliation: Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
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: D000818:Animals; D002065:Buspirone / Q000494:pharmacology*; D002395:Catecholamines / Q000097:blood*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000097:blood; D007101:Immersion; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D013315:Stress, Psychological / Q000097:blood*
chemical_list: D002395:Catecholamines; D002707:Chlordiazepoxide; D002065:Buspirone; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine