As a framework for beginning to define the organization of stress-related peptide systems in relation to addiction, Fig. 4 provides a schematic of neurocircuitry that drives drug seeking and taking [adapted from (Koob and Volkow, 2010)]. Into the schematic are integrated key nodes where the modulators discussed in our review can act to promote relapse and drug taking under stressful, aversive conditions (red colors). Some information to begin outlining this organization is available. For example, N/OFQ appears to reduce stress-induced alcohol seeking and escalated consumption through anti-stress actions within local central amygdala circuitry, where it presumably directly opposes CRF / CRF1R actions (Economidou et al., 2008). Ucn/CRF2R systems interact with dynorphin within the amygdala, but can also exert their influence at the level of the dorsal raphe (Vuong et al., 2010), a structure that is activated by stress and sends serotonergic projects to both amygdala and nucleus accumbens. Ucn/CRF2R activity can also modulate the activity of the lateral septum, which projects to both amygdala and hypothalamus, and whose activity promotes active stress coping and suppresses endocrine stress responses (Singewald et
