L-DOPA provides the most potent medication to treat Parkinson's disease, and 
such systemic treatment is usually combined with a peripheral amino acid 
decarboxylase inhibitor to amplify its central effectiveness. Since L-DOPA can 
lose its efficacy or can lead to adverse effects with prolonged application, 
current pharmacokinetic and dynamic research is aimed at improving the drug's 
applicability. In a previous study, performed with in vivo microdialysis in the 
anesthetized rat, we have shown that intranasal L-DOPA administration (without 
prior decarboxylase inhibition) can increase extracellular dopamine levels in 
the neostriatum. Using similar experimental conditions in the present 
experiment, we tested the neurochemical effects of L-DOPA treatment in 
combination with the peripheral amino acid decarboxylase inhibitor benserazide. 
In accordance with other data, it was found that the combination of i.p. 
benserazide and i.p. L-DOPA led to pronounced increases of extracellular levels 
of dopamine, dihydroxyplenylacetic acid and homovanillic acid in the 
neostriatum, whereas i.p. L-DOPA alone only moderately increased dopamine, but 
strongly increased the metabolite levels. Furthermore, increased dopamine 
levels, and weaker increases of dihydroxyplenylacetic acid and homovanillic acid 
were observed after i.p. benserazide followed by intranasal L-DOPA. Finally, we 
found that i.p. benserazide alone can lead to pronounced increases in 
neostriatal dopamine and moderate increases of dihydroxyplenylacetic acid 
levels, whereas it did not affect homovanillic acid. Thus, not only the 
combination of L-DOPA (i.p. or intranasal) with the presumed peripheral L-DOPA 
decarboxylase inhibitor benserazide, but also each component alone can affect 
dopamine activity in the brain. Especially the findings with benserazide 
treatment might be of relevance for understanding the mechanisms of current 
L-DOPA therapy, since they indicate that part of the treatment's actions may 
possibly be determined by central dopaminergic effects of the accompanying amino 
acid decarboxylase inhibitor.