Blue-181, a non-narcotic, small molecule, binds to a novel CNS drug target. Blue-181 is being developed as an analgesic that will be devoid of the serious side-effects associated with the use of opioid painkillers. One of the most important of these problems is addictive potential. To investigate the possible reinforcing (rewarding) effects of Blue-181, we determined whether it would maintain self-administration in rats that had been trained to intravenously (i.v.) self-administer heroin. Heroin, a µ-opioid agonist and a Schedule 2 controlled drug (C-II), was selected as the positive control. Saline was the non-reinforcing control. Butorphanol, which is a mixed μ/κ-opioid receptor partial agonist, was the reference comparator. Butorphanol was selected because it has very low potential for human abuse and is not a controlled drug in the UK.