in the HPA-axis and extended amygdala (Koob, 2008). Both stress- and drug-induced activation of the HPA-axis allows glucocorticoids to sensitize reward pathways, characterized by increases in reward thresholds during withdrawal (Koob and Kreek, 2007). As dependence and withdrawal develop, brain “anti-reward” systems, such a CRF, are recruited in the extended amygdala (Koob, 2013a) contributing to dysphoria and distress. Thus, the motivation to take drugs is not only driven by conditioned response cues, but by negative emotional states.
