Evaluation of L-DOPA biotransformation during repeated L-DOPA infusion into the striatum in freely-moving young and old rats.
The aim of this study was to assess changes in L-3, 4-dihydroxyphenylalanine (L-DOPA) biotransformation in response to two-pulse infusion of L-DOPA into the striatum of freely-moving young (3-4 month) and old (21-26 month) male Wistar rats. In addition, the effects of L-DOPA infusion on the vesicular dopamine (DA) store in young rats were also studied. Both L-DOPA-induced DA overflow and uptake of the perfused L-DOPA by the striatum were used to study L-DOPA biotransformation during microdialysis. High potassium-induced DA depletion was performed to assess the dynamics of the vesicular DA store following L-DOPA infusion. Concentric microdialysis probes were stereotaxically implanted in the lateral striatum of rats of both age groups and microdialysis was begun 24 h later. All rats received 2x20 min infusions of 3 mgr L-DOPA separated by an interval of 60 min. In the striatum of both groups, L-DOPA-induced DA overflow and uptake of exogenous L-DOPA were both significantly enhanced during the second infusion compared to the first. In young rats, when a 20-min infusion of 3 mgr L-DOPA was given between 2x20 min infusions of 100 mM potassium, no increased DA release was seen at the second high potassium challenge compared with the first. Our results suggest that the enhancement of DA overflow induced by the second L-DOPA infusion is, at least partially, due to an increase in L-DOPA biotransformation, and not simply to an enlarged DA pool. In contrast to the in vitro results, our own in vivo results show that L-DOPA utilization in the aging striatum does not deteriorate with age.
Shui
H
H
Department of Physiology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Road, 10018, Taipei, Taiwan.
Peng
Y
Y
Wu
R
R
Tsai
Y
Y
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D007980:Levodopa / Q000493:pharmacokinetics*; D008124:Locomotion; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar
D000978:Antiparkinson Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D006719:Homovanillic Acid