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
William A
WA
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA. carlezon@mclean.harvard.edu
Mague
Stephen D
SD
Parow
Aimee M
AM
Stoll
Andrew L
AL
Cohen
Bruce M
BM
Renshaw
Perry F
PF
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000178:diet therapy / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013550:Swimming / Q000523:psychology*; D013997:Time Factors; D014529:Uridine / Q000627:therapeutic use*
D000928:Antidepressive Agents; D015525:Fatty Acids, Omega-3; D014529:Uridine