Changes in brain striatum dopamine and acetylcholine receptors induced by chronic CDP-choline treatment of aging mice.R. Giménez, J. Raïch, and J. AguilarDepartment of Biochemistry, Faculty of Pharmacy, University of Barcelona, Spain.
Abstract1. Spiroperidol binding (dopamine D2 receptors) and quinuclidinyl benzilate binding (muscarinic receptors) in striata of 19-month old mice was analyzed for animals that had received chronic administration of cytidine 5'-diphosphocholine (CDP-choline) incorporated into the chow consumed (100 or 500 mg kg-1 added per day) for the 7 months before they were killed.
2. Treated animals displayed an increase in the dopamine receptor densities of 11% for those receiving 100 mg kg-1 and 18% for those receiving 500 mg kg-1 as compared to the control aged animals that had received no CDP-choline. Control animals showed, from 2 months to 19 months of life, a 28% decrease in the receptor density. No change in the affinity of the receptors for spiroperidol was found in the treated or untreated animals.
3. Muscarinic acetylcholine receptor densities were also partially recovered by the same treatment in aged animals that showed a 14% decrease of these receptors in this case. The muscarinic receptor density increased 6% for the animals that received 100 mg kg-1 and 17% for the animals that received 500 mg kg-1 without any change in the affinity of the receptor for quinuclidinyl benzilate.
4. Aged animals displayed a slight increase in brain membrane fluidity as indicated by a decrease in the polarization value of the non-polar fluorophore 1,6-diphenyl-1,3,5-hexatriene. Interestingly, in the treated animals a greater increase in membrane fluidity was determined and found to be very similar for the two doses.
5 It is concluded that chronic administration of CDP-choline to aged animals promoted a partial
recovery of the striatum dopamine and acetylcholine receptor function normally reduced with aging,
which might be explicable in terms of mechanisms involving fluidity of the brain neuronal membrane.
Keywords: Muscarinic receptor; dopamine D2 receptor; aging; striatum; choline donor; CDP-choline (cytidine
5'-diphosphocholine); membrane fluidity