The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis

Dmitry Zaretsky, Maria V. Zaretskaia, Sumit Sarkar, Daniel Rusyniak, Joseph A. DiMicco

Research output: Contribution to journalArticle

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Abstract

The corticotropin-releasing hormone (CRH) plays an important role in mediating physiological response to stress and is thought to be involved in the development of various psychiatric disorders. In this paper, we compare the differences between the effect of intraperitoneal (i.p.) and intraarterial (i.a.) administration of the non-peptide CRH1 antagonist CP-154,526 (CP) (10 and 20 mg/kg) on plasma adrenocorticotropic hormone levels (ACTH), heart rate, MAP, and c-Fos expression in the paraventricular nucleus of the hypothalamus. Intraperitoneal, but not i.a., injection of CP resulted in an increase in plasma ACTH (from 105 ± 13 to 278 ± 51 pg/ml after 20 mg/kg). This effect was accompanied by a dramatic increase in c-Fos expression in cells immunoreactive for CRH in the paraventricular nucleus of the hypothalamus. When the drug was administered i.p., CP-induced activation of the HPA appears to mask the inhibitory effect of CP on stress-induced ACTH secretion, an effect which was readily apparent when the drug was given i.a. Intraperitoneal administration of CP also increased the baseline MAP which may account for previous reports that treatment with this drug attenuated the increases associated with stress. CP given by either route had no effect on baseline heart rate or stress-induced tachycardia. Thus, in all studies in which CP 154,526 is given, the route of delivery must be given careful consideration.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalNeuroscience Letters
Volume653
DOIs
StatePublished - Jul 13 2017

Fingerprint

Adrenocorticotropic Hormone
Paraventricular Hypothalamic Nucleus
Corticotropin-Releasing Hormone
Hypothalamus
Heart Rate
Pharmaceutical Preparations
Intra-Arterial Injections
Physiological Stress
Masks
Tachycardia
Psychiatry
CP 154526
Therapeutics
quinterenol

Keywords

  • Blood pressure
  • CRH antagonist
  • HPA axis
  • Stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

The non-peptide CRH1-antagonist CP-154,526 elicits a paradoxical route-dependent activation of the HPA axis. / Zaretsky, Dmitry; Zaretskaia, Maria V.; Sarkar, Sumit; Rusyniak, Daniel; DiMicco, Joseph A.

In: Neuroscience Letters, Vol. 653, 13.07.2017, p. 1-6.

Research output: Contribution to journalArticle

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