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.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.Lipids. 1996; 31: S157-161
- Chronic citicoline increases phosphodiesters in the brains of healthy older subjects.Psychopharmacology. 2002; 161: 248-254
- Is the forced swimming test a suitable model for revealing antidepressant activity?.Psychopharmacol. 1988; 94: 147-160
- The relationship between alpha-tocopherol and phospholipid fatty acids in rat liver subcellular membrane fractions.Biochem Biophys Acta. 1988; 962: 81-90
- Antidepressant-like effects of cytidine in the forced swim test in rats.Biol Psychiatry. 2002; 51: 882-889
- The effects of dietary omega-3 polyunsaturated fatty acids on erythrocyte membrane phospholipids, erythrocyte deformability and blood viscosity in healthy volunteers.Atherosclerosis. 1985; 55: 267-281
- A randomized efficacy trial of citicoline in patients with acute ischemic stroke.Stroke. 1999; 30: 2592-2597
- Finding the intracellular signaling pathways affected by mood disorder treatments.Neuron. 2003; 38: 157-160
- Brain metabolic alterations in medication-free patients with bipolar disorder.Arch Gen Psychiatry. 2004; 61: 450-458
- Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants.Psychopharmacol. 1995; 121: 66-72
- Depression.Biol Psychiatry. 2004; 56: 140-145
- A molecular and cellular theory of depression.Arch Gen Psychiatry. 1997; 54 (597–60)
- Omega-3 polyunsaturated fatty acid levels in the diet and in red blood cell membranes of depressed patients.J Affect Disord. 1998; 48: 149-155
- The hippocampus in patients treated with electroconvulsive therapy.Arch Gen Psychiatry. 2000; 57: 937-943
- Cell signalling through guanine-nucleotide-binding regulatory proteins (G proteins) and phospholipases.Eur J Biochem. 1997; 243: 10-20
- Omega-3 fatty acids in psychiatry.Ann Clin Psychiatry. 2000; 12: 159-165
- Lipid fluidity markedly modulates the binding of serotonin to mouse brain membranes.Proc Natl Acad Sci USA. 1980; 77: 7463-7467
- Fish consumption and major depression.Lancet. 1998; 351: 1213
- Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics.Biol Psychiatry. 1998; 44: 235-242
- Omega-3 fatty acid treatment decreases T2 whole brain relaxation times in bipolar disorder.Am J Psychiatry. 2004; 161: 1922-1924
- Mitochondrial dysfunction in bipolar disorder.Bipolar Disord. 2000; 2: 180-190
- Molecular evidence for mitochondrial dysfunction in bipolar disorder.Arch Gen Psychiatry. 2004; 61: 300-308
- Enhancement of free fatty acid incorporation into phospholipids by choline plus cytidine.Brain Res. 1999; 822: 52-55
- Biochemistry and physiology of ω-3 fatty acids.FASEB J. 1992; 6: 2530-2536
- Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing.Am J Obstet Gynecol. 2003; 188: 1348-1353
- Omega-3 fatty acids in major depression.World Rev Nutr Diet. 2001; 89: 173-185
- Evidence that 5’-cytidinediphosphocholine can affect brain phospholipid composition by increasing choline and cytidine plasma levels.J Neurochem. 1995; 65: 889-894
- Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients.Psychiatry Res. 1999; 85: 275-291
- Omega-3 fatty acids for the prevention of postpartum depression.Depress Anxiety. 2004; 19: 20-23
- A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression.Am J Psychiatry. 2003; 160: 996-998
- Effects of cytidine-5’-diphosphocholine on norepinephrine, dopamine and serotonin synthesis in various regions of the rat brain.Arch Int Pharmacodyn. 1979; 239: 52-56
- Choline, myo-inositol and mood in bipolar disorder.Bipolar Disord. 2000; 3: 207-216
- Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects.Am J Psychiatry. 1997; 154: 116-118
- Addition of omega-3 fatty acid to maintenance medication treatment for recurrent unipolar depressive disorder.Am J Psychiatry. 2002; 159: 477-479
- Antidepressant treatments in the 21st century.Biol Psychiatry. 1998; 44: 526-533
- Preclinical models.Biol Psychiatry. 2002; 52: 503-528
- A long-lasting facilitation of hippocampal neurotransmission via a phospholipase A2 signaling pathway.Life Sci. 2001; 68: 2885-2891
- Phosphoinositide signaling in human brain.Prog Neurobiol. 1996; 50: 255-273
- A dose-ranging study of the effects of ethyl-eicosapentaenoate in patients with ongoing depression despite apparently adequate treatment with standard drugs.Arch Gen Psychiatry. 2002; 59: 913-919
- Depletion of omega-3 fatty acid levels in red blood cell membranes of depressive patients.Biol Psychiatry. 1998; 43: 315-319
- Altered responsiveness to cocaine and increased immobility in the forced swim test associated with elevated cAMP response element binding protein expression in nucleus accumbens.J Neurosci. 2001; 21: 7397-7403
- Effect of dietary cod-liver oil on the lipid composition of human erythrocyte membranes.Scand J Clin Lab Invest. 1984; 44: 39-46
- Depression.Nature. 1977; 266: 730-732
- Hypothyroidism and thyroxin substitution affect the n-3 fatty acid composition of rat liver mitochondria.Lipids. 1991; 26: 781-787
- Short-term treatment with citicoline (CDP-choline) attenuates some measures of craving in cocaine-dependent subjects.Psychopharmacol. 1999; 142 (132–13)
- Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells.Brain Res. 2003; 971: 161-167
- CDP-choline.Methods Find Clinical Pharmacol. 1995; 17: 1-54
- Lack of effect of eicosapentaenoic acid in the Porsolt forced swimming test model of depression.Acta Neuropsychiatrica. 2002; 14: 203-206
- Identification of two molecular species of rat brain phosphatidylcholine that rapidly incorporate and turn over arachidonic acid in vivo.J Neurochem. 1996; 67: 1702-1710
- Compounds containing cytosolic choline in the basal ganglia.Am J Psychiatry. 1999; 156: 1638-1640
- Increased orbitofrontal cortex levels of choline in depressed adolescents as detected by in vivo proton magnetic resonance spectroscopy.Biol Psychiatry. 2000; 48: 1053-1061
- Omega 3 fatty acids in bipolar disorder.Arch Gen Psychiatry. 1999; 56: 407-412
- Omega-3 fatty acids in major depressive disorder. A preliminary double-blind, placebo-controlled trial..Eur Neuropsychopharmacol. 2003; 13: 267-271
- Fish consumption, depression, and suicidality in a general population.Arch Gen Psychiatry. 2001; 58: 512-513
- Fish consumption and depressive symptoms in the general population in Finland.Psychiatr Serv. 2001; 52: 529-531
- The validity of animal models of depression.Psychopharmacol. 1984; 83: 1-16
- Effect of oral CDP-choline on plasma choline and uridine levels in humans.Biochem Pharmacol. 2000; 60: 989-992
Article Info
Publication History
Published online: January 25, 2005
Accepted:
November 22,
2004
Received in revised form:
November 15,
2004
Received:
August 20,
2004
Identification
Copyright
© 2005 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
