INCREASED NEOSTRIATAL DOPAMINE ACTIVITY AFTER INTRAPERITONEAL OR INTRANASAL ADMINISTRATION OF L-DOPA - ON THE ROLE OF BENSERAZIDE PRETREATMENT

L-DOPA provides the most potent medication to treat Parkinson's diseas e, and such systemic treatment is usually combined with a peripheral a mino acid decarboxylase inhibitor to amplify its central effectiveness . Since L-DOPA can lose its efficacy or can lead to adverse effects wi th prolonged application, current pharmacokinetic and dynamic research is aimed at improving the drugs applicability. In a previous study, p erformed with in vivo microdialysis in the anesthetized rat, we have s hown that intranasal L-DOPA administration (without prior decarboxylas e inhibition) can increase extracellular dopamine levels in the neostr iatum. Using similar experimental conditions in the present experiment , we tested the neurochemical effects of L-DOPA treatment in combinati on with the peripheral amino acid decarboxylase inhibitor benserazide. Ln accordance with other data, it was found that the combination of i .p. benserazide and i.p. L-DOPA led to pronounced increases of extrace llular levels of dopamine, dihydroxyplenylacetic acid and homovanillic acid in the neostriatum, whereas i.p. L-DOPA alone only moderately in creased dopamine, but strongly increased the metabolite levels. Furthe rmore, increased dopamine levels, and weaker increases of dihydroxyple nylacetic acid and homovanillic acid were observed after i.p. benseraz ide followed by intranasal L-DOPA. Finally, we found that i.p. bensera zide drone can lead to pronounced increases in neostriatal dopamine an d 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 decarbox ylase inhibitor benserazide, but also each component alone can affect dopamine activity in the brain. Especially the findings with benserazi de treatment might be of relevance for understanding the mechanisms of current L-DOPA therapy, since they indicate that part of the treatmen t's actions may possibly be determined by central dopaminergic effects of the accompanying amino acid decarboxylase inhibitor. (C) 1997 Wile y-Liss, Inc.