Evaluation of periodic limb movements in a putative animal model of restless leg syndrome§

Authors

  • Cleide Lopes MS,

    1. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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    • Dr. Lopes and Dr. Esteves contributed equally to this work.

  • Andrea M. Esteves PhD,

    1. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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    • Dr. Lopes and Dr. Esteves contributed equally to this work.

  • Roberto Frussa-Filho PhD,

    1. Department of Pharmacology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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  • Sergio Tufik PhD,

    1. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
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  • Marco Tulio de Mello PhD

    Corresponding author
    1. Department of Psychobiology, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
    • Department of Psychobiology, Universidade Federal de São Paulo, Rua Francisco de Castro, 93, Vila Clementino, São Paulo, SP, Brazil
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  • Funding agencies: This work was supported by grants from Associação Fundo de Incentivo à Pesquisa (AFIP), Coordenação de Aperfeiçoamento de Pessoal de Nível Supeior (CAPES), and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #08/50646-6 to A.M.E. and CEPID no. 98/14303-3 to S.T.).

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Restless leg syndrome (RLS) is a major healthcare burden with increasing prevalence. It has been demonstrated that periodic limb movements (PLM) can occur as an isolated phenomenon, but they are often associated with this syndrome and are the only symptom of this disorder that can be measured electrophysiologically. The aim of this study was to examine the sleep-wake behavior and the presence of limb movement in a rat model of RLS induced by lesioning the A11 dopaminergic nuclei with the neurotoxin 6-hydroxydopamine (6-OHDA). Rats were implanted with electrodes for electrocorticography and electromyography. Sleep recordings were monitored during light/dark periods lasting 12 hours each and were evaluated on days 7, 15, and 28 after injection of the drug or phosphate-buffered saline (PBS). A control group that did not receive any injection was also included. Wakefulness percentages were generated for 4-hour segments of the dark period, yielding the following 3 bins: 7 PM to 11 PM, 11 PM to 3 AM, and 3 PM to 7 PM. Additionally, slow wave sleep, paradoxical sleep, wakefulness, and limb movements were evaluated over the entire 12 hours of the light/dark cycle. All A11-lesioned rats exhibited an increased percentage of wakefulness during the last block of the dark period, as would be expected for an animal model of this syndrome. In addition, at all time points after lesioning, these animals presented increased frequencies of limb movement during both the light and the dark periods. These alterations were reversed by the acute administration of the dopaminergic agonist pramipexole. This animal model strengthens the notion that 6-OHDA–induced A11 lesions can be a valid animal model for RLS and PLM. © 2011 Movement Disorder Society

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