Brain benzodiazepine receptor-mediated effects on plasma catecholamine and corticosterone concentrations in rats.
The effects of the benzodiazepine (BDZ) receptor agonist chlordiazepoxide (CDP) and antagonist flumazenil (Ro 15-1788), given alone and in combination, on basal and novel environment stress (NES)-elevated plasma noradrenaline (NA), adrenaline (A) and corticosterone (CS) contents were investigated. When administered on their own, a medium dose of CDP (2.5 mg/kg) and a moderate dose of flumazenil (5 mg/kg) did not affect basal hormone levels. However, flumazenil potentiated the NES-induced CS elevation and suppressed the NA rise in response to NES. The 2.5 mg/kg dose of CDP attenuated the NES-elicited rise of CS and A, without changing the NES-enhanced NA concentrations. High doses of CDP (10 and 12.5 mg/kg), which elevated basal CS levels, prevented a further CS increase by NES and completely abolished the NA and A response to NES. The CDP effects on CS and NA were antagonized by pretreatment with flumazenil, in contrast to the CDP effect on A which was not blocked. The data indicate that brain (central-type) BDZ receptor systems are involved in regulating the neurosympathetic and adrenocortical, but not adrenomedullary, responses to mild stress.
De Boer
S F
SF
Department of Psychopharmacology, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Van der Gugten
J
J
Slangen
J L
JL
D000818:Animals; D002395:Catecholamines / Q000097:blood*; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000378:metabolism*
D002395:Catecholamines; D011963:Receptors, GABA-A; D005442:Flumazenil; D002707:Chlordiazepoxide; D003345:Corticosterone