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 dopami ne, but serotonin (5-HT) is also reduced. Because 5-HT decreases follo wing a single levodopa injection, levodopa has been suggested to contr ibute to PD's serotonergic deficits. However, in a recent study, rat s triatal serotonin levels were reported to increase following 15-day le vodopa administration. To address this issue, we administered levodopa (50 mg/kg) to rabbits for 5 days, then measured serotonin, its precur sors tryptophan and 5-hydroxytryptophan (5-HTP), and its major metabol ite 5-hydroxyindole-acetic acid (5-HIAA) in striatum and CSF:. Striata l serotonin and tryptophan were unchanged, while 5-HTP and 5-HIAA incr eased 4- and 7-fold, respectively. CSF 5-HTP and 5-HIAA were also sign ificantly increased. In levodopa-treated animals, 5-HTP concentrations were moderately correlated (r = 0.679) between striatum and CSF, whil e weak correlations were present between striatal and CSF concentratio ns of both serotonin and 5-HIAA. These results suggest that repeated l evodopa treatment increases striatal serotonin turnover without changi ng serotonin content. However, levodopa-induced alterations in striata l serotonin metabolism may not be accurately reflected by measurement of serotonin and 5-HIAA in CSF.