Effects of Morphine and Alcohol on the Hypothalamic–Pituitary–Adrenal Axis, Immunity, and Cognitive Behavior

Abstract

The hypothalamic–pituitary–adrenal (HPA) axis is a feedback loop that includes the hypothalamus, pituitary, and adrenal glands. The HPA axis has been shown to regulate immune responses. The main hormones involved in the HPA axis are corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and glucocorticoids (GC), which are also called stress hormones. These hormones contribute to the regulation of immune responses and can also affect neuronal survival, neurogenesis, synaptic plasticity, and behavioral responses [1, 2]. The HPA axis is a three-tiered biological system that begins at the highest level with the release of CRH from the hypothalamic paraventricular nucleus (PVN). CRH-expressing neurons located in the PVN of the hypothalamus play a pivotal role in orchestrating the central stress response. CRH stimulates the release of ACTH from the anterior pituitary gland. In turn, ACTH acts on the adrenal cortex to increase the production and release of GC hormones. Proper functioning of all of these neurons is essential for maintaining a homeostatic state following a stressful event. Several neuronal pathways modulate HPA axis activity. For example, the hippocampus and prefrontal cortex inhibit the HPA axis, and the amygdala and monoaminergic input from the brainstem stimulate CRH production by PVN neurons. GC hormones exert negative feedback control of the HPA axis by binding to GC receptors on hippocampal and hypothalamic PVN neurons [3–5].