Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats

Background: Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. We showed previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (FST) in rats, a model used in depression research. Because cytidine and uridine both stimulate synthesis of cytidine 5'-diphosphocholine (CDP-choline, a critical substrate for phospholipid synthesis), we examined whether uridine would also produce antidepressant-like effects in rats. We also examined the effects of omega-3 fatty acids (OMG), which increase membrane fluidity and reportedly have antidepressant effects in humans, alone and in combination with uridine. Methods: We first examined the effects of uridine injections alone and dietary supplementation with OMG alone in the FST. We then combined subjective treatment regimens of uridine and OMG to determine whether these agents would be more effective if administered together. Results: Uridine dose-dependently reduced immobility in the FST, an antidepressant-like effect. Dietary supplementation with OMG reduced immobility when given for 30 days, but not 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effiective dietary supplementation with OMG. Conclusions: Uridine and OMG each have antidepressant-like effects in rats. Less of each agent is required for effectiveness when the treatments are administered together.