The opiate receptor-like 1 receptor for the neuropeptide nociceptin shows high homology to opioid receptors and plays an important role in inhibition of the rewarding effects of addictive drugs. The opiate receptor-like 1 receptor couples to inhibitory G proteins and negatively regulates the function of the mesolimbic dopaminergic system. Studies suggest that the endogenous nociceptin system has a role in mediating responses to alcohol (Murphy 2010). Oprl1 knockout rats are more sensitive to the rewarding effect of morphine than wild-type controls (Rutten et al. 2011). Oprl1 knockout mice displayed increased anxiety-related behavior (Gavioli et al. 2007) and nociceptin blocked the development of cocaine-induced locomotor sensitization in mice (Bebawy et al. 2010). In humans, reduction in PNOC mRNA (1.7-fold) in the hippocampus and OPRL1 mRNA (1.4-fold) in the central amygdala of postmortem brain of alcoholics, compared with controls, was reported (Kuzmin et al. 2009).
