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 effects of THC in several conditional lines has revealed implication of the CB1 receptor expressed at the level of forebrain glutamatergic neurons (CB1CamKIIa-Cre mice), cortical glutamatergic neurons (CB1NEX-Cre mice) and dopaminergic neurons (CB1Drd1a-Cre mice), but not GABAergic neurons (CB1Dlx5/6-Cre mice) (Monory et al., 2007). Also a conditional knockout approach using Pet1-Cre mice, targeting the transcription factor Lmx1b in developing serotonergic neurons of the hindbrain, showed that central serotonergic neurons modulate supraspinal pain but are not involved in morphine reward (Zhao et al., 2007). So far, only one conditional line has been reported for opioid receptors and peptides, demonstrating a key role of delta receptors expressed in primary nociceptive neurons in delta analgesia and the control of chronic pain (Gaveriaux-Ruff et al., 2011). It is expected that conditional lines for the opioid system, targeting the neurocircuitry of addiction, will be instrumental to understand circuit mechanisms underlying opioid-mediated drug effects and plasticity.
