EFFECTS OF SEROTONERGIC AGENTS ON FOOD-RESTRICTION-INDUCED HYPERACTIVITY

Rats that are fed for 90 min per day can stabilize their weight after an initial drop; however, if rats on this feeding schedule are also gi ven access to a running wheel, they run excessively, eat less, lose we ight, and often die. To investigate this phenomenon as a possible anim al model of obsessive-compulsive disorder (OCD), rats were treated for 5 weeks with fluoxetine, an antidepressant that relieves OCD symptoms in humans (5 mg/kg, 2.5 mg/kg), or imipramine, an antidepressant that does not affect OCD symptoms (5 mg/kg), or saline prior to exposure t o food restriction and the running wheel. In addition, because chronic fluoxetine treatment is thought to enhance serotonergic neurotransmis sion, for contrast an additional group of rats were treated with parac hlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor that dep letes serotonin. Rats treated with fluoxetine lost significantly less weight, ran significantly less, and increased food intake more rapidly during restriction of food availability than saline-treated rats. Rat s treated with imipramine did not differ from those treated with salin e on these parameters. Compared to saline-treated rats, rats treated w ith PCPA lost more weight, ate less food, and increased running more r apidly. These effects of pharmacological treatment indicate an inverse relationhip between central serotonergic activity and vulnerability t o develop food-restriction-induced anorexia and compulsive running. In addition, like OCD in humans, this phenomenon in rats seems to be blo cked by chronic treatment with a serotonin selective reuptake inhibito r but not a less selective monoamine reuptake inhibitor.