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

M. E. Keck; T. Welt; M. B. Müller; R. Landgraf; F. Holsboer

doi:10.1055/s-2003-38092

Pharmacopsychiatry, Table of Contents

Pharmacopsychiatry 2003; 36(1): 27-31
DOI: 10.1055/s-2003-38092

Original Paper

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

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

Full Text

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Dr. Martin E. Keck

Max Planck Institute of Psychiatry

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