Establishment of an ethanol vs midazolam vs water three-choice discrimination in rats

Drug discrimination procedures that require discriminations based on two different drugs and the absence of any drug effects (3-choice discriminations) are relatively rare. One potential use of these discriminations is to characterize how similar the discriminative stimulus effects of two drugs are in relation to each other. Our lab has used this discrimination procedure to classify similarities between ethanol and other ligands that act at the GABAA receptor. In the present study we tested whether we could establish an ethanol vs. midazolam vs. water discrimination. Adult male Long-Evans rats (n=12) were trained to discriminate midazolam (3.0 mg/kg; i.p.) from ethanol (1.0 g/kg; i.g.) from water (2.3 ml; i.g.) in a 3 lever, food-reinforced task. The average number of training sessions required to train the 3-choice discrimination was 105 (± 16). The establishment of this discrimination is novel and should be a useful tool to ethanol-like effects of GABAA positive modulators, NMDA antagonists and 5-HT1 agonists in a discrimination that forces a more specific receptor basis for the ethanol cue.