Attenuation of food-restriction-induced running by chronic fluoxetine treatment

In rats, 90-minute daily access to food is sufficient to maintain or even increase body weight. However, when rats are provided with access to a running wheel for the remaining portion of the day, progressive increases in activity and decreases in weight reach life-threatening proportions within 1-2 weeks. To investigate this phenomenon as a possible animal model of obsessive-compulsive disorder (OCD), rats were treated i.p. daily for 5 weeks with fluoxetine, an antidepressant that relieves OCD symptoms; imipramine, an antidepressant that does not affect OCD symptoms; or saline prior to exposure to food restriction and the running wheel. Compared with saline-treated controls, rats treated with fluoxetine showed significant attenuation of wheel running, anorexia, and weight loss. However, rats treated with imipramine did not differ from saline-treated controls on any measures. These results indicate that food-restriction-induced compulsive running and the associated anorexia are selectively prevented by treatment with an antidepressant that blocks serotonin reuptake. This raises the possibility that this repetitive, maladaptive behavior may be a valid animal model for OCD.