Rats are trained to discriminate between a drug of abuse (e.g., cocaine) and vehicle in a two - lever food-reinforced procedure. Following training, rats are tested with an experimental drug to determine whether generalization ('substitution') to the drug of abuse cue occurs, indicative of potential abuse liability and a shared pharmacological target. Alternatively, rats could be trained to discriminate between an experimental compound and vehicle, and substitution tests with various drugs of abuse (cocaine, d-amphetamine, etc.) could be run for generalization. An experimental compound that substitutes but is not self-administered could indicate a possible treatment for addiction.
In addition to assessing potential abuse liability, the DD assay is a valuable assay of in vivo pharmacological mechanism(s) of action. For example, various GABAA receptor legends exhibited distinct profiles in rats trained to discriminate chlordiazepoxide (CDP) or zolpidem from vehicle.
Finally, the DD assay may also be used to assess pharmacodynamic profiles of novel compounds. For example, the time-course of the nicotine discriminative stimulus was assessed in rats trained to discriminate nicotine (0.4 mg/kg IP) from saline when administered 10 minutes before testing.