The conceptual challenges for drug development in this area are more interesting and perhaps also more challenging. First, an understanding of how these systems are organized and interact will be critical for assessing their therapeutic potential. If, for instance, urocortin and dynorphin signalling are indeed organized in series as proposed, with kappa opioid receptor activation downstream of Ucn/CRF2R activity in a final common pathway of stress reactivity (Bruchas et al., 2010), then therapeutics targeting CRF2R may have little to offer beyond those that block kappa opioid receptors, and are further along in clinical development. However, other urocortin pathways also contribute to addiction-related behaviors, leaving the possibility that additive effects may be possible.
