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

Abstract

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.

• Authors: William A Carlezon Jr, Stephen D Mague, Aimee M Parow, Andrew L Stoll, Bruce M Cohen, Perry F Renshaw
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 57 Issue 4 Pg. 343-50 (Feb 15 2005) ISSN: 0006-3223 [Print] United States
• PMID: 15705349 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antidepressive Agents
• Fatty Acids, Omega-3
• Uridine

Topics

• Animals
• Antidepressive Agents (pharmacology, therapeutic use)
• Behavior, Animal (drug effects)
• Depression (diet therapy, drug therapy)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Drug Synergism
• Drug Therapy, Combination
• Fatty Acids, Omega-3 (administration & dosage)
• Immobility Response, Tonic (drug effects)
• Male
• Motor Activity (drug effects)
• Rats
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Swimming (psychology)
• Time Factors
• Uridine (therapeutic use)