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

Citation
M. Vythilingam et al., Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: Effects of yohimbine and naloxone, J CLIN END, 85(11), 2000, pp. 4138-4145
Citations number
52
Categorie Soggetti
Endocrynology, Metabolism & Nutrition","Endocrinology, Nutrition & Metabolism
Journal title
JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN journal
0021972X → ACNP
Volume
85
Issue
11
Year of publication
2000
Pages
4138 - 4145
Database
ISI
SICI code
0021-972X(200011)85:11<4138:CFCHIH>2.0.ZU;2-N
Abstract
CRH neurons projecting from the paraventricular nucleus (PVN) of the hypoth alamus 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 s tress response and may play a role in mood and anxiety disorders. We have a ttempted to investigate possible noradrenergic and opioid regulation of the se non-HPA CRH neurons. We hypothesized that yohimbine (an alpha (2)-adrene rgic antagonist) would have stimulatory action on non-HPA CRH neurons, wher eas naloxone (a mu -opioid receptor antagonist) would not have this effect. Adult normal volunteers received iv yohimbine (n = 5; 0.4 mug/kg), naloxon e (n = 4; 125 mug/kg), or placebo (n = 3; 0.9% saline). Cerebrospinal fluid (CSF) was collected continuously, and concentrations of CSF CRH, CSF norep inephrine (NE), and plasma cortisol were measured. Administration of either yohimbine or naloxone caused significant increases in plasma cortisol conc entrations over time. Although yohimbine robustly increased CSF NE levels a nd appeared to increase CSF CRH levels, these effects were not seen after n aloxone or placebo administration. Intraindividual correlations were not ob served between the measured concentrations of plasma cortisol and CSF CRH f or any of the subjects. The results support the idea that CSF CRH concentra tions reflect the activity of non-HPA CRH neurons. Although both yohimbine and naloxone stimulated the HPA axis, only yohimbine appeared to have stimu latory effects on central NE and non-HPA CRH.