Effects of buspirone and chlordiazepoxide on plasma catecholamine and corticosterone levels in stressed and nonstressed rats.
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.
De Boer
S F
SF
Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Slangen
J L
JL
Van der Gugten
J
J
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*
D002395:Catecholamines; D002707:Chlordiazepoxide; D002065:Buspirone; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine