The interaction of opioid system with multiple pathways involved in the stress response. The figure published originally by Lovallo (33) indicates that areas where opioid blockade acts in three areas: 1) the periventricular nucleus of the hypothalamus (PVN), the locus ceruleus, and the nucleus accumbens. Opioids normally stimulate DA release by the nucleus accumbens, inhibits CRF release from the PVN, and inhibit release of norepinephrine from the locus ceruleus (22). Reprinted from the International Journal of Psychophysiology, Vol. 59, Issue 3, Pages 195–202, William Lovallo, Cortisol secretion patterns in addiction and addiction risk (2006), with permission from Elsevier.