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Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: On the role of benserazide pretreatment

1997; Wiley; Volume: 27; Issue: 4 Linguagem: Inglês

10.1002/(sici)1098-2396(199712)27

1098-2396

M.A. de Souza Silva, Claudia Mattern, R. H�cker, Carlos Tomaz, J.P. Huston, Rainer K.W. Schwarting,

Olfactory and Sensory Function Studies

SynapseVolume 27, Issue 4 p. 294-302 Increased neostriatal dopamine activity after intraperitoneal or intranasal administration of L-DOPA: On the role of benserazide pretreatment M.A. de Souza Silva, M.A. de Souza Silva Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, Germany Department of Psychobiology, University of São Paulo, Ribeirão Preto, BrasilSearch for more papers by this authorC. Mattern, C. Mattern Mattern et Partner, 82319 Starnberg, GermanySearch for more papers by this authorR. Häcker, R. Häcker Mattern et Partner, 82319 Starnberg, GermanySearch for more papers by this authorC. Tomaz, C. Tomaz Department of Psychobiology, University of São Paulo, Ribeirão Preto, BrasilSearch for more papers by this authorJ.P. Huston, J.P. Huston Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, GermanySearch for more papers by this authorR.K.W. Schwarting, Corresponding Author R.K.W. Schwarting rainer.schwarting@uni.duesseldorf.de Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Physiological Psychology I, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, GermanySearch for more papers by this author M.A. de Souza Silva, M.A. de Souza Silva Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, Germany Department of Psychobiology, University of São Paulo, Ribeirão Preto, BrasilSearch for more papers by this authorC. Mattern, C. Mattern Mattern et Partner, 82319 Starnberg, GermanySearch for more papers by this authorR. Häcker, R. Häcker Mattern et Partner, 82319 Starnberg, GermanySearch for more papers by this authorC. Tomaz, C. Tomaz Department of Psychobiology, University of São Paulo, Ribeirão Preto, BrasilSearch for more papers by this authorJ.P. Huston, J.P. Huston Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, GermanySearch for more papers by this authorR.K.W. Schwarting, Corresponding Author R.K.W. Schwarting rainer.schwarting@uni.duesseldorf.de Institute of Physiological Psychology I, and Biologisch-Medizinisches Forschungszentrum, Heinrich-Heine-University of Düsseldorf, 40225 Düsseldorf, GermanyInstitute of Physiological Psychology I, Heinrich-Heine-University of Düsseldorf, Universitätsstr. 1, 40225 Düsseldorf, GermanySearch for more papers by this author First published: 07 December 1998 https://doi.org/10.1002/(SICI)1098-2396(199712)27:4 3.0.CO;2-7Citations: 33AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract 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. Synapse 27:294–302, 1997. © 1997 Wiley-Liss, Inc. Citing Literature Volume27, Issue4December 1997Pages 294-302 RelatedInformation