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01-07-2009 | Movement Disorders - Original Article

Noradrenergic modulation of the motor response induced by long-term levodopa administration in Parkinsonian rats

Authors: Virgili Pérez, Victoria Sosti, Antonia Rubio, Manel Barbanoj, Ignasi Gich, José Rodríguez-Álvarez, Jaime Kulisevsky

Published in: Journal of Neural Transmission | Issue 7/2009

Abstract

A decrease in noradrenergic activity in Parkinson’s disease might play a critical role in long-term motor complications associated with chronic dopaminergic replacement. Using the rat model of parkinsonism with an additional noradrenergic degeneration induced by the N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) toxin we evaluated whether the circling motor activity and dose-failure episodes induced by levodopa (l-DOPA) differ between single (6-OHDA) and double (6-OHDA + DSP-4) denervated animals challenged with a single daily dose of l-DOPA. While single-lesioned animals showed a sensitization–desensitization turning response with a significant increase on day 15 and a decrease on day 22, in double-lesioned animals, the turning activity was maximal from day 1 and did not decay on day 22. Double-lesioned rats exhibited significantly higher number of turns on days 15 and 22 and a significantly lower percentage of dose-failure episodes during treatment. Noradrenergic denervation appears to be associated with prolonged long-term dopaminergic sensitization. This type of response appears to be comparable to that in the clinical setting with intermittent l-DOPA administration where no desensitization occurs once the abnormal response is established.

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Title: Noradrenergic modulation of the motor response induced by long-term levodopa administration in Parkinsonian rats
Authors: Virgili Pérez
Victoria Sosti
Antonia Rubio
Manel Barbanoj
Ignasi Gich
José Rodríguez-Álvarez
Jaime Kulisevsky
Publication date: 01-07-2009
Publisher: Springer Vienna
Published in: Journal of Neural Transmission / Issue 7/2009
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-009-0242-9

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Noradrenergic modulation of the motor response induced by long-term levodopa administration in Parkinsonian rats

Abstract

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Abstract

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