Confirmation of abuse liability comes from training rats to self-administer an experimental compound. Rats are trained to self-administer cocaine (or another drug of abuse such as nicotine) by lever-pressing in an operant box. Once rats exhibit stable drug intake, the training drug can be substituted by an experimental compound. If the experimental drug is self-administered this indicates potential drug abuse liability. In such a case, drug-naïve rats can then be tested to assess whether the compound is self-administered in subjects that have no prior drug experience, providing stronger evidence for the abuse liability of the novel compound.

(A) A dose-response function for nicotine self-administration where every nicotine infusion requires 3 active lever presses. (B) Nicotine self-administration is sensitive to blockade of nicotinic acetylcholine receptors, but not dopamine reuptake blockade. Also, the anti-smoking medication varenicline (Chamtix ®) decreased nicotine self-administration.