Skip to main content
Journal cover image

Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.

Publication ,  Journal Article
Smith, CC; Hauser, E; Renaud, NK; Leff, A; Aksentijevich, S; Chrousos, GP; Wilder, RL; Gold, PW; Sternberg, EM
Published in: Brain Res
January 13, 1992

We have previously demonstrated that susceptibility of Lewis (LEW/N) rats to inflammatory disease, compared to relatively resistant Fischer (F344/N) rats, is related to deficient glucocorticoid counter-regulation of the immune response resulting from deficient corticotropin-releasing hormone (CRH) responsiveness to inflammatory and other stress mediators. The GABA/benzodiazepine receptor complex is an important negative modulator of CRH secretion and responsiveness to excitatory stimuli. In this study, we have examined in vitro binding of [3H]flunitrazepam to hypothalamic membrane preparations from LEW/N and F344/N rats. LEW/N rats had significantly more hypothalamic benzodiazepine binding sites (Bmax) than F344/N rats, but there were no differences in benzodiazepine binding affinities (Kd) between these two strains. The differences in benzodiazepine receptor number were consistent with the respective plasma corticosterone levels in the two strains, and with previous work indicating a negative correlation between corticosterone levels and benzodiazepine binding site number. Adrenalectomy of F344/N rats increased benzodiazepine binding to levels comparable to LEW/N animals and treatment of adrenalectomized F344/N rats with DEX resulted in lowering of benzodiazepine Bmax to levels that did not differ significantly from those of intact F344/N rats. There was no significant change in receptor number in either adrenalectomized or DEX-treated LEW/N rats. These findings suggest that basal benzodiazepine receptor differences between these strains may be partially related to strain differences in corticosterone levels, however that additional factors may contribute to maintenance of these differences in LEW/N rats. Since benzodiazepines attenuate hypothalamic CRH secretion through GABAergic inhibition, we suggest that strain differences in receptor number could also augment strain differences in hypothalamic-pituitary-adrenal axis function through differential sensitivity to GABA-mediated feedback.

Duke Scholars

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

January 13, 1992

Volume

569

Issue

2

Start / End Page

295 / 299

Location

Netherlands

Related Subject Headings

  • Species Specificity
  • Receptors, GABA-A
  • Rats, Inbred Lew
  • Rats, Inbred F344
  • Rats
  • Pituitary-Adrenal System
  • Neurology & Neurosurgery
  • Male
  • Kinetics
  • Hypothalamus
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Smith, C. C., Hauser, E., Renaud, N. K., Leff, A., Aksentijevich, S., Chrousos, G. P., … Sternberg, E. M. (1992). Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats. Brain Res, 569(2), 295–299. https://doi.org/10.1016/0006-8993(92)90642-m
Smith, C. C., E. Hauser, N. K. Renaud, A. Leff, S. Aksentijevich, G. P. Chrousos, R. L. Wilder, P. W. Gold, and E. M. Sternberg. “Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.Brain Res 569, no. 2 (January 13, 1992): 295–99. https://doi.org/10.1016/0006-8993(92)90642-m.
Smith CC, Hauser E, Renaud NK, Leff A, Aksentijevich S, Chrousos GP, et al. Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats. Brain Res. 1992 Jan 13;569(2):295–9.
Smith, C. C., et al. “Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats.Brain Res, vol. 569, no. 2, Jan. 1992, pp. 295–99. Pubmed, doi:10.1016/0006-8993(92)90642-m.
Smith CC, Hauser E, Renaud NK, Leff A, Aksentijevich S, Chrousos GP, Wilder RL, Gold PW, Sternberg EM. Increased hypothalamic [3H]flunitrazepam binding in hypothalamic-pituitary-adrenal axis hyporesponsive Lewis rats. Brain Res. 1992 Jan 13;569(2):295–299.
Journal cover image

Published In

Brain Res

DOI

ISSN

0006-8993

Publication Date

January 13, 1992

Volume

569

Issue

2

Start / End Page

295 / 299

Location

Netherlands

Related Subject Headings

  • Species Specificity
  • Receptors, GABA-A
  • Rats, Inbred Lew
  • Rats, Inbred F344
  • Rats
  • Pituitary-Adrenal System
  • Neurology & Neurosurgery
  • Male
  • Kinetics
  • Hypothalamus