Conventional knockout approaches have proved valuable to tease apart respective contributions of opioid receptor and peptides in several aspects of drug abuse. Further important developments in addiction research involve investigation of molecular mechanisms operating at the level of neuronal circuits underlying the distinct aspects of addiction (Koob and Volkow, 2010). Therefore, genetic approaches targeted at specific brain sites or neuronal populations are required (Fowler and Kenny, 2012; Gaveriaux-Ruff and Kieffer, 2007; Heldt and Ressler, 2009), among which conditional gene knockout using the Cre/loxP system has received great attention (Nagy, 2000). In the addiction field, several studies using this technology have provided invaluable insights into circuit mechanisms of drug reward. Site-specific deletion of α4-containing nAChR (McGranahan et al., 2011) as well as NMDA receptor NR1 subunit (Wang et al., 2010) has revealed involvement of NMDA receptors expressed in dopaminergic neurons in nicotine reward. Mice lacking CREB specifically in the cerebral cortex were tested for cocaine self-administration and showed a role for CREB in mediating cocaine reinforcement in this brain structure (McPherson et al., 2010). A comprehensive analysis of behavioral and autonomic
