Effect of acetyl-L-carnitine on the dopaminergic system in aging brain.
We studied the effect of acetyl-L-carnitine (ALCAR) on dopamine release and the effect of long-term acetyl-L-carnitine treatment on age-related changes in striatal dopamine receptors and brain amino acid levels. In striatal tissue that had been incubated with [3H]dopamine, acetyl-L-carnitine increased the release of [3H]dopamine evoked by electrical stimulation. In striatal tissue from aged mice administered acetyl-L-carnitine for 3 months, the release of [3H]dopamine evoked by electrical stimulation was higher than that of its aged control; the release after a second stimulation was similar in the two groups. There was a significant decline in the number of D1 striatal dopamine receptors with age. The Bmax was 51% lower in 1.5-year-old mice than in 4-month-old animals. Administration of acetyl-L-carnitine for 3 months diminished the reduction in the binding of [3H]SCH-23390. [3H]Spiperone binding to D2 receptors was not decreased with age and was not affected by acetyl-L-carnitine treatment. Age-related decreases in levels of several amino acids were observed in several brain regions. Acetyl-L-carnitine lessened the reduction in the level of taurine only in the striatum. The findings confirm the multiple effects of acetyl-L-carnitine in brain, and suggest that its administration can have a positive effect on age-related changes in the dopaminergic system.
Sershen
H
H
Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York 10962.
Harsing
L G
LG
Banay-Schwartz
M
M
Hashim
A
A
Ramacci
M T
MT
Lajtha
A
A
D000108:Acetylcarnitine / Q000378:metabolism / Q000494:pharmacology*; D000375:Aging; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2
D000596:Amino Acids; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D000108:Acetylcarnitine; D004298:Dopamine