Although typically associated with approach behaviors, the VTA is also engaged in stress-induced reinstatement of drug seeking. It has been reported that intra-VTA CRF2R blockade dampens stress-induced reinstatement of cocaine seeking (Wang et al., 2007), but another study failed to replicate these results (Blacktop et al., 2011). In this report, both CRF- and footshock-stress-induced reinstatement of cocaine seeking were blocked by VTA injections of two different selective CRF1R antagonists but not two CRF2R antagonists. Furthermore, the CRF1R selective agonist cortagine but not the CRF2R selective agonist Ucn2 replicated the effects of CRF to reinstate cocaine seeking. These data are in agreement with previous findings that systemic or ICV injections of CRF1R but not CRF2R antagonists block stress-induced reinstatement (Lu et al., 2003). Taken together, a clear role of CRF2R and urocortins in cocaine-seeking behavior is yet to be established.
