SEROTONIN AND THE REGULATION OF HYPOTHALAMIC-PITUITARY-ADRENAL AXIS FUNCTION

That serotonin (5HT) is involved in regulating hypothalamic-pituitary- adrenal axis (HPA) function has long been recognized. A variety of dru gs including precursors of 5HT such as 5HTP, drugs which release 5HT s uch as fenfluramine and drugs which act directly on 5HT receptors such as ipsapirone increase cortisol and ACTH concentrations. There is a g eneral assumption that such stimulation occurs at a hypothalamic level . However, our increasing understanding of the complex interplay betwe en 5HT and the HPA raises questions as to the validity of this simple model. An increasing volume of experimental research indicates that 5H T can act directly on the adrenal gland and possibly on the anterior p ituitary as well. These findings have major implications for the inter pretation of neuroendocrine studies of 5NT conducted in psychiatric co nditions, such as depression.