Cerebrospinal Fluid Corticotropin-Releasing Hormone in Healthy Humans: Effects of Yohimbine and Naloxone

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 (anα 2-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 (NE), and plasma cortisol were measured. Administration of either yohimbine or naloxone caused significant increases in p...