Phenytoin: similarity to tricyclic antidepressants

Rats were trained to discriminate between the stimulus properties of intraperitoneal injections of 10 mg/kg phenytoin and its pH-adjusted vehicle in a two-lever, food-motivated operant task. Once trained, rats showed a dose-related decrease in discriminative performance with lower phenytoin doses. Administration of pentobarbital and chlordiazepoxide produced vehicle-appropriate responding, whereas injection of imipramine and amitriptyline produced intermediate results. Desipramine, at an intraperitoneal dose of 10 mg/kg, produced a pattern of responding similar to that observed after the training dose of phenytoin. These results demonstrate, for the first time, the ability of a non-disruptive dose of phenytoin to act as a behavioral discriminative stimulus in the rat and suggest the possibility of a common interoceptive cue property with tricyclic antidepressants.