title: Corticosteroid feedback resistance in rats genetically selected for increased dopamine responsiveness.
abstract: Pharmacogenetically selected Wistar rat lines were used to investigate the implication of either high or low responsiveness of the dopamine system for the activity of the hypothalamus-pituitary-adrenal (HPA) axis. As selection criterion the gnawing response induced by the dopamine agonist apomorphine was used. This criterion allows to distinguish apomorphine susceptible (apo-sus) rats which show a vigorous gnawing response from apomorphine unsusceptible (apo-unsus) rats. The present study, using male animals of the 9-12th generation of the two rat lines, revealed the following characteristics of the stress response system: (i) in apo-sus rats under basal conditions corticotrophin-releasing hormone (CRH) mRNA level in the paraventricular nucleus (PVN) and plasma adrenocorticotropin (ACTH) concentration were significantly higher; total corticosterone (B) plasma level was similar but free B level was lower; (ii) exposure to a novel environment resulted in a higher and prolonged plasma ACTH and total B response in the apo-sus rats. Moreover, the elevated free B level was also prolonged; (iii) apo-sus rats had increased CRH-induced pituitary ACTH release and B secretion was also increased, but not as prolonged as during novelty. (iv) In dexamethasone-pretreated rats an intravenous ACTH1-24 injection resulted in a similar plasma B response in rats of both lines; (v) In vitro, ACTH1-24 produced a significantly higher B secretion by adrenocortical cells of apo-sus rats reflecting the higher in vivo ACTH priming of the adrenal glands in these animals. (vi) apo-sus rats had higher body and thymic weight.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
authors.forename: N Y
authors.initials: NY
authors.lastname: Rots
authors.forename: A R
authors.initials: AR
authors.lastname: Cools
authors.forename: J
authors.initials: J
authors.lastname: de Jong
authors.forename: E R
authors.initials: ER
authors.lastname: De Kloet
mesh_terms: D000305:Adrenal Cortex Hormones / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D005246:Feedback; D006624:Hippocampus / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D008297:Male; D010913:Pituitary-Adrenal System / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D012641:Selection, Genetic
chemical_list: D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D004298:Dopamine; D003345:Corticosterone