Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: Effects of yohimbine and naloxone

Meena Vythilingam, George M. Anderson, Michael J. Owens, Thomas M. Halaszynski, J. Douglas Bremner, Linda L. Carpenter, George R. Heninger, Charles Nemeroff, Dennis S. Charney

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Abstract

CRH neurons projecting from the paraventricular nucleus (PVN) of the hypothalamus to the median eminence control hypothalamic-pituitary-adrenal (HPA) axis activity. However, CRH neurons outside the PVN as well as PVN neurons projecting to sites other than the median eminence also contribute to the stress response and may play a role in mood and anxiety disorders. We have attempted to investigate possible noradrenergic and opioid regulation of these non-HPA CRH neurons. We hypothesized that yohimbine (an α2-adrenergic antagonist) would have stimulatory action on non-HPA CRH neurons, whereas naloxone (a μ-opioid receptor antagonist) would not have this effect. Adult normal volunteers received iv yohimbine (n = 5; 0.4 μg/kg), naloxone (n = 4; 125 μg/kg), or placebo (n = 3; 0.9% saline). Cerebrospinal fluid (CSF) was collected continuously, and concentrations of CSF CRH, CSF norepinephrine (HE), and plasma cortisol were measured. Administration of either yohimbine or naloxone caused significant increases in plasma cortisol concentrations over time. Although yohimbine robustly increased CSF HE levels and appeared to increase CSF CRH levels, these effects were not seen after naloxone or placebo administration. Intraindividual correlations were not observed between the measured concentrations of plasma cortisol and CSF CRH for any of the subjects. The results support the idea that CSF CRH concentrations reflect the activity of non-HPA CRH neurons. Although both yohimbine and naloxone stimulated the HPA axis, only yohimbine appeared to have stimulatory effects on central NE and non-HPA CRH.

Original languageEnglish
Pages (from-to)4138-4145
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume85
Issue number11
DOIs
StatePublished - Dec 1 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Vythilingam, M., Anderson, G. M., Owens, M. J., Halaszynski, T. M., Bremner, J. D., Carpenter, L. L., Heninger, G. R., Nemeroff, C., & Charney, D. S. (2000). Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: Effects of yohimbine and naloxone. Journal of Clinical Endocrinology and Metabolism, 85(11), 4138-4145. https://doi.org/10.1210/jc.85.11.4138