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 sub-effective 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 for 3 or 10 days. A sub-effective dose of uridine reduced immobility in rats given sub-effective 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.
Carlezon, WA; Mague, SD; Parow, AM; Stoll, AL; Cohen, BM; Renshaw, PF
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