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 al., 2011). SP/NK1Rs promote stress responses, and are positioned to drive negatively reinforced drug seeking through actions at the level of the dorsal raphe, lateral septum, and amygdala (Ebner et al., 2008a). Finally, release of NPS, whose activation of NPSR suppresses anxiety-like behavior (Xu et al., 2004), has recently been shown within the basolateral amygdala in response to stress (Ebner et al., 2011). A further layer of complexity is added by the fact that, in addition to their stress modulating actions, urocortins, SP, N/OFQ, and NPS can also influence drug seeking through pathways mediating positively reinforcing drug effects (shown in green in Fig. 4). Finally, emerging data indicate that the habenula (not shown in the figure), a structure that is rich in NK1R receptors, may be at the intersection of “reward” and “anti-reward” pathways, and negatively reinforce behavior through inputs to the VTA (Stamatakis and Stuber, 2012).
