Activation of the hypothalamic-pituitary-adrenal (HPA) axis plays an integral role in responses to stress. Following a stressor, corticotropin-releasing factor (CRF) is released from the paraventricular nucleus (PVN) of the hypothalamus, stimulating POMC synthesis in the pituitary and the release of two POMC metabolites: adrenocorticotropic hormone (ACTH) and β-endorphin. Acting on the adrenal glands, ACTH stimulates the release of glucocorticoids (cortisol in primates and corticosterone in rodents; CORT), which can then have many central and peripheral effects. MOPRs located on CRF neurons in the PVN serve to tonically inhibit HPA axis stimulation; thus, differences in endogenous opioid transmission or receptor activity can alter basal CORT levels or stress-mediated CORT responses. Just as genetic differences can affect response to drugs (pharmacogenetics), alterations in responses to an individual’s own biologically active compounds (physiogenetics) are influenced by genetic differences (Kreek and LaForge, 2007). Indeed, individuals with the G118 allele have baseline elevations in CORT levels (Bart et al., 2006; Hernandez-Avila et al., 2003). Several studies have shown that the CORT-response to a behavioral stressor is lower in G118 allele-carriers (Chong et al., 2006; Pratt and Davidson, 2009).
