Central nervous system-acting drugs influencing hypothalamic-pituitary-adrenal axis function

The hypothalamic-pituitary-adrenal (HPA) axis is a major integrated system that maintains body homeostasis by regulating the neuroendocrine and sympathetic nervous systems and modulating immune function. It is well established that the central nervous system (CNS) integrates responses to different stimuli secreting a specific corticotropin-releasing hormone (CRH) and vasopressin (AVP). In turn, they stimulate the release of ACTH, which induces steroidogenesis in the adrenal gland. The HPA axis is regulated by diurnal rhythms and negative feedback by corticosteroids. Many neurotransmitters and neuropeptides are responsible for the modulation of CRH and AVP neurons. In addition to synthetic glucocorticoids that inhibit the HPA axis, GABA agonists, opioid peptides and endocannabinoids can inhibit cortisol secretion. On the contrary, serotonin, norepinephrine, dopamine, acetylcholine, ghrelin, angiotensin II and different cytokines can stimulate it. It follows that a number of neuroactive drugs, acting as agonists or antagonists on several brain neurotransmitter or neuropeptide receptors, can influence ACTH/cortisol secretion thereby interfering with clinical testing of the functionality of the HPA axis