Effects of CDP-choline on striatal dopamine level and behavior in rats.
To further assess the effects of CDP (cytidine diphosphate)-choline on Parkinsonian symptoms, striatal dopamine (DA) was measured fluorometrically in rats after injection of CDP-choline. CDP-choline (300 mg/kg, i.p.) increased the DA content in the striatum (p less than 0.05) one hour after injection. The behavioral effect of CDP-choline was then tested in rats in which the unilateral nigro-striatal DA neurons had degenerated following an intranigral injection of 6-hydroxydopamine (6-OHDA). CDP-choline alone did not produce behavioral changes in these rats. However, pretreatment with a single dose of CDP-choline (900 mg/kg, i.p.) suppressed both the apomorphine-induced contralateral and the d-amphetamine-induced ipsilateral circling. The same dose of CDP-choline suppressed the number of treadmill revolutions in mice. On the other hand, a 7-day consecutive treatment with 300 mg/kg of CDP-choline enhanced the apomorphine-induced contralateral circling (by 42%, p less than 0.05). The same treatment with CDP-choline raised the striatal DA content by 29% (p less than 0.05) on the intact side, but not on the 6-OHDA injected side. These results indicate that CDP-choline has either a direct nor an indirect DA agonistic effect. The increase in DA content, decrease in locomotion and enhancement of the effect of apomorphine can be explained on the hypothesis that CDP-choline may act as an antagonist on the DA neurons and receptors. The validity of this apparently paradoxical use of CDP-choline with antagonistic effect on DA neurons in the treatment of Parkinson's disease is discussed.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002794:Choline / Q000031:analogs & derivatives*; D003342:Corpus Striatum / Q000032:analysis* / Q000187:drug effects; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D006892:Hydroxydopamines / Q000494:pharmacology; D008297:Male; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects
D006892:Hydroxydopamines; D011954:Receptors, Dopamine; D003566:Cytidine Diphosphate Choline; D002794:Choline; D004298:Dopamine