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Overproduction of corticotropin-releasing factor in transgenic mice - a genetic model of anxiogenic behavior

Academic Article
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Overview

authors

  • Stenzelpoore, M. P.
  • Heinrichs, S. C.
  • Rivest, S.
  • Koob, George
  • Vale, W. W.

publication date

  • May 1994

journal

  • Journal of Neuroscience  Journal

abstract

  • Corticotropin-releasing factor (CRF) is released in response to various stressors and regulates adrenocorticotropin secretion and glucocorticoid production. In addition to its endocrine functions, CRF acts as a neuromodulator in extra-hypothalamic systems and has been shown to play a role in behavioral responses to stress. CRF overproduction has been implicated in affective disorders such as depression and anorexia nervosa. A transgenic mouse model of CRF overproduction has been developed in order to examine the endocrine and behavioral effects of chronic CRF excess. CRF transgenic animals exhibit endocrine abnormalities involving the hypothalamic-pituitary-adrenal axis such as elevated plasma levels of ACTH and glucocorticoids. The present series of experiments tested the hypothesis that chronic overproduction of CRF throughout the life-span of these animals may lead to an anxiogenic behavioral state. CRF transgenic mice and normal littermate controls were tested by measuring locomotor activity in a novel environment and through the use of an elevated plus-maze as indices of anxiety. CRF transgenic animals exhibited an increase in anxiogenic behavior, an effect known to occur following central administration of CRF in mice and rats. Injection of the CRF antagonist alpha-helical CRF 9-41 into the lateral cerebral ventricles reversed the anxiogenic state observed in the CRF transgenics. This finding supports the possibility that central CRF overproduction may mediate the anxiogenic behavior exhibited in this animal model. Thus, CRF transgenic mice represent a genetic model of CRF overproduction that provides a valuable tool for investigating the long-term effects of CRF excess and dysregulation in the CNS.

subject areas

  • Adrenocorticotropic Hormone
  • Animals
  • Anxiety
  • Cerebral Ventricles
  • Corticotropin-Releasing Hormone
  • Glucocorticoids
  • Hypothalamo-Hypophyseal System
  • Infusions, Parenteral
  • Injections, Intraventricular
  • Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Models, Genetic
  • Motor Activity
  • Peptide Fragments
  • Pituitary-Adrenal System
  • Rats
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Research

keywords

  • ACTH
  • ANXIOGENIC
  • BEHAVIOR
  • CORTICOTROPIN-RELEASING FACTOR
  • DEPRESSION
  • GLUCOCORTICOIDS
  • RODENTS
  • TRANSGENIC
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Identity

International Standard Serial Number (ISSN)

  • 0270-6474

PubMed ID

  • 8182429
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Additional Document Info

start page

  • 2579

end page

  • 2584

volume

  • 14

issue

  • 5

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