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
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.