CRF2 as well as CRF1 and receptors are present within the dorsal raphe (DR) nucleus, a structure that modulates behavioral stress responses through serotonergic projections to widespread target areas in the forebrain (Waselus et al., 2011). CRF1 and CRF2 receptors have opposing effects on serotonin (5-HT) release in projection areas of serotonergic DR neurons (Lukkes et al., 2008). Withdrawal from chronic stimulants is associated with increased sensitivity to stress and negative emotional states both in humans and animals, and these states are thought to contribute to increased relapse vulnerability. The CRF2R was found to be elevated in the DR following chronic amphetamine treatment (Pringle et al., 2008), and intra-DR CRF2R blockade dampened the enhanced anxiety-like behavior observed during amphetamine withdrawal (Vuong et al., 2010). This suggests that CRF2R antagonists may have a potential to prevent motivational consequences of negative emotional states and CRF2R up-regulation resulting from stimulant use.
