Among these biologically active peptides, ACTH and β-endorphin are two principal components of the hypothalamic-pituitary-adrenal (HPA) axis. ACTH mediates the stress response in vertebrates (5). Stress induces the secretion of corticotropin-release hormone (CRH) from the hypothalamus, which stimulates ACTH synthesis and release from the anterior pituitary. ACTH, in turn, promotes the release of glucocorticoids (e.g, cortisol, a major stress hormone) from the adrenal cortex. Through negative feedback, glucocorticoids regulate the expression of CRH and ACTH. β-endorphin, an endogenous opioid peptide exerting potent analgesic and euphoric effects through interaction with opioid receptors, is made in neurons of the brain stem, as well as those in the hypothalamus and pituitary. It produces behavioral effects similar to exogenous opioids and is released in the nucleus accumbens (NAc), the major brain reward center (6). Based on these actions, both ACTH and β-endorphin have been implicated in craving use of drugs and alcohol (7).
