Influence of repeated levodopa administration on rabbit striatal serotonin metabolism, and comparison between striatal and CSF alterations.
Parkinson's disease (PD) is characterized by decreased striatal dopamine, but serotonin (5-HT) is also reduced. Because 5-HT decreases following a single levodopa injection, levodopa has been suggested to contribute to PD's serotonergic deficits. However, in a recent study, rat striatal serotonin levels were reported to increase following 15-day levodopa administration. To address this issue, we administered levodopa (50 mg/kg) to rabbits for 5 days, then measured serotonin, its precursors tryptophan and 5-hydroxytryptophan (5-HTP), and its major metabolite 5-hydroxyindole-acetic acid (5-HIAA) in striatum and CSF. Striatal serotonin and tryptophan were unchanged, while 5-HTP and 5-HIAA increased 4- and 7-fold, respectively. CSF 5-HTP and 5-HIAA were also significantly increased. In levodopa-treated animals, 5-HTP concentrations were moderately correlated (r = 0.679) between striatum and CSF, while weak correlations were present between striatal and CSF concentrations of both serotonin and 5-HIAA. These results suggest that repeated levodopa treatment increases striatal serotonin turnover without changing serotonin content. However, levodopa-induced alterations in striatal serotonin metabolism may not be accurately reflected by measurement of serotonin and 5-HIAA in CSF.
Loeffler
D A
DA
Clinical Neuroscience Program, Sinai Hospital, Detroit, MI 48235, USA.
LeWitt
P A
PA
Juneau
P L
PL
Camp
D M
DM
DeMaggio
A J
AJ
Havaich
M K
MK
Milbury
P E
PE
Matson
W R
WR
D006916:5-Hydroxytryptophan / Q000134:cerebrospinal fluid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D012701:Serotonin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D014364:Tryptophan / Q000134:cerebrospinal fluid / Q000378:metabolism
D012701:Serotonin; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D006916:5-Hydroxytryptophan