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We examined the effects of orally administered 5'-cytidinediphosphocholine (CDP-choline) on arterial plasma choline and cytidine levels and on brain phospho- lipid composition in rats . Animals receiving a single oral dose of 100, 250, or 500 mg/kg showed peak plasma choline levels 6-8 h after drug administration (from 12 1 to 17 ± 2, 19 ± 2, and 24 ± 2 pM, respectively) . The area under the plasma choline curve at >14 IiM,i.e., at a concentration that induces a net influx of choline into the brain, was significantly correlated with CDP-choline dose .In rats receiving 500 mg/kg this area was 2 .3 times that of animals consuming 250 mg/kg, which in turn was 1 .8 times that of rats receiving 100 mg/kg . Plasma cyti- dine concentrations increased 5 .4, 6 .5, and 15 .1 times baseline levels, respectively, 8 h after each of the three doses . When the oral CDP-choline treatment was pro- longed for 42 and 90 days, brain phosphatidylcholine concentrations increased significantly (by 22-25% ; p < 0 .05) in rats consuming 500 mg/kg/day . Brain phos- phatidylethanolamine and phosphatidylserine concentra- tions also increased significantly under some experi- mental conditions ; levels of other phospholipids were

Experiments were performed to determine whether exogenous cytidine (5′) diphosphocholine (CDP-choline) could modify the release of dopamine (DA) in the striatum. Rats were divided into two groups, receiving either a standard diet (UAR 004) or the same diet supplemented with CDP-choline (250 mg/kg day) for 28 days. On the last day the dialysis probes were inserted in the striatum, and DA, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid (DOPAC) efflux were measured in the dialysis stream basally and during K+depolarization (80 mM K+). Basal DA, HVA, and DOPAC did not show any difference between treated and untreated groups. Depolarization with K+ increased DA levels by up to 3,000% in the control group and by up to 4,770% in the CDP-choline-treated group (p

A passive avoidance procedure was used to measure the ability to learn and remember to avoid a noxious stimulus in 13-month-old mice and to test the effects that treatment with cytidine(5')-diphosphocholine (CDP-choline) had on these processes. Half of the mice received 500 mg/kg per day CDP-choline orally for 4 months, and the two groups were compared with a third group of younger animals (4-month-old mice). The older mice showed marked impairment in the execution of these tests; however, those treated with CDP-choline had significant improvement in their performance 24 hours after learning the task.

Cytidine, as cytidine 5'-diphosphate choline (CDP-choline), is important for the synthesis of phosphatidylcholine in cell membranes. To investigate whether exogenous CDP-choline could affect brain phospholipid composition, we supplemented the diet of mice with this drug (500 mg/kg/day) for 27 months in 3-month-old mice and for 90, 42, and 3 days in 12-month-old mice, and measured their levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), and the content of phosphatidylinositol plus phosphatidic acid in the cerebral cortex. After 27 months of treatment, PC and PE increased significantly by 19% (P0.05) and by 20% (P0.01), respectively. PS levels increased by 18% (not statistically significant). Similar elevations in PC and PE levels were obtained when older mice were treated for only 3 months (P0.05). No changes were observed with shorter treatment periods. These results suggest that chronic administration of CDP-choline can have effects on brain phospholipid composition that may underlie its reported utility in various neurologic disorders.