addiction, shows that mu receptors remain a prime target in most successful treatments for addiction (Pierce et al., 2012). Delta agonists may be efficient to limit disruption of emotional responses in addicted individuals (Lutz and Kieffer, 2012). Delta drugs have been developed to treat chronic pain and depression, and are currently being tested in the clinic, but their use in indications related to drug abuse has not been considered, as yet (Gaveriaux-Ruff and Kieffer, 2011). Preclinical research has definitely established that kappa receptor activity plays a role in addiction-related behaviors, with a prodepressant-like activity (see review (Lutz and Kieffer, 2013). Kappa antagonists are therefore promising candidates for pharmacotherapies in stress- and addiction-related disorders, and may attenuate compulsive drug intake (Wee and Koob, 2010) or specific symptoms of depressive disorders, depending on the administration time point (Knoll and Carlezon, 2010). Finally, considering the growing evidence of comorbidity between addiction and depression, possible improvement of addiction therapies may arise from the combination of substitution treatments (mu agonists such as methadone, or partial agonists such as buprenorphine) with kappa antagonists or delta agonists, for treating patients with comorbid conditions (Lutz and Kieffer, 2013).
