Antidepressant-like effects of cytidine in the forced swim test in rats.
BACKGROUND
Altered brain phospholipid metabolism may be involved in the pathophysiology of cocaine dependence and mood disorders. Evidence suggests that citicoline, a rate-limiting metabolite for phospholipid synthesis, reduces cocaine craving in human addicts. Because antidepressants can reduce cocaine craving, we explored in rats the possibility that citicoline has antidepressant effects. We also tested the primary metabolites of citicoline, cytidine and choline.


METHODS
We examined if citicoline or metabolites alter immobility in the forced swim test. We used two scoring methods: latency to become immobile, a simple method that identifies antidepressants, and behavioral sampling, a complex method that differentiates antidepressants according to pharmacological mechanisms.


RESULTS
Over a range of doses, citicoline did not affect behavior in the forced swim test. At molar equivalent doses, cytidine dramatically decreased immobility, whereas choline tended to increase immobility. The effects of cytidine resemble those of desipramine, a standard tricyclic antidepressant. None of the treatments affected locomotor activity, and cytidine did not establish conditioned place preferences.


CONCLUSIONS
Citicoline does not have effects in the forced swim test, but its primary metabolites have opposing effects: cytidine has antidepressant-like actions, whereas choline has prodepressant-like actions. At antidepressant doses, cytidine lacks stimulant and rewarding properties. This is the first report of potential antidepressant effects of cytidine.
Carlezon
William A
WA
Department of Psychiatry, Harvard Medical School, McLean Hospital, Belmont, Massachusetts 02478, USA.
Pliakas
Andrea M
AM
Parow
Aimee M
AM
Detke
Michael J
MJ
Cohen
Bruce M
BM
Renshaw
Perry F
PF
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003042:Cocaine; D003562:Cytidine / Q000494:pharmacology*; D003566:Cytidine Diphosphate Choline / Q000378:metabolism / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming
D000928:Antidepressive Agents; D003566:Cytidine Diphosphate Choline; D003562:Cytidine; D003042:Cocaine; D003891:Desipramine