Abstract
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.
Keywords
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Article info
Publication history
Accepted:
October 31,
2001
Received in revised form:
October 24,
2001
Received:
August 16,
2001
Identification
Copyright
© 2002 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
