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Pharmacopsychiatry 2003; 36(1): 27-31
DOI: 10.1055/s-2003-38092
Original Paper
© Georg Thieme Verlag Stuttgart · New York

The High-affinity Non-peptide CRH1 Receptor Antagonist R121919 Attenuates Stress-induced Alterations in Plasma Oxytocin, Prolactin, and Testosterone Secretion in Rats

M. E. Keck1 , T. Welt1 , M. B. Müller1 , R. Landgraf1 , F. Holsboer1
  • 1Max Planck Institute of Psychiatry, Munich, Germany
Further Information

Publication History

Received: 20.2.2002 Revised: 11.4.2002

Accepted: 6.6.2002

Publication Date:
21 March 2003 (online)

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Abstract

Evidence from basic and clinical research suggests that hyperactivity of central corticotropin-releasing hormone (CRH) circuits contributes to causality and course of affective disorders. Therefore, CRH receptor antagonists have attracted attention as potential therapeutics. We could previously show that the novel high-affinity non-peptide CRH1 receptor antagonist R121919 significantly inhibits stress-induced corticotropin release and displays anxiolytic effects in rats selectively bred for high anxiety-related behavior. These animals are characterized by their innate hyper-reactivity of the hypothalamic-pituitary-adrenocortical system linked to an increased emotionality and therefore are suitable for the evaluation of CRH1 receptor antagonists. Here we show that in addition to its effects on anxiety-related behavior and corticotropin secretion, R121919 attenuates the stress-induced release of corticosterone, prolactin, and oxytocin. Moreover, the decrease in plasma testosterone following exposure to stress is abolished by R121919. Our data indicate that antagonism of CRH1 receptors may prevent stress-associated endocrine alterations.

Key words

Antidepressant - stress - depression - corticotropin-releasing hormone - corticotropin-releasing factor - corticotropin-releasing hormone receptor antagonist - testosterone - prolactin - oxytocin

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Dr. Martin E. Keck

Max Planck Institute of Psychiatry

Kraepelinstr. 2-10

D-80804 Munich

Germany

Phone: +49-89-30622-314

Fax: +49-89-30622-569

Email: keck@mpipsykl.mpg.de