Journal of Neural Transmission

, Volume 115, Issue 10, pp 1385–1392

Continuous versus pulsatile administration of rotigotine in 6-OHDA-lesioned rats: contralateral rotations and abnormal involuntary movements

  • Werner J. Schmidt
  • Heike Lebsanft
  • Manfred Heindl
  • Manfred Gerlach
  • Edna Gruenblatt
  • Peter Riederer
  • Andreas Mayerhofer
  • Dieter K. A. Scheller
Basic Neurosciences, Genetics and Immunology - Original Article

DOI: 10.1007/s00702-008-0102-z

Cite this article as:
Schmidt, W.J., Lebsanft, H., Heindl, M. et al. J Neural Transm (2008) 115: 1385. doi:10.1007/s00702-008-0102-z

Abstract

Sustained drug delivery providing continuous dopaminergic stimulation is thought to prevent or delay the induction of motor complications (dyskinesia) in Parkinson’s disease, whereas pulsatile administration is supposed to promote them. This study investigated the inducibility of sensitization and abnormal involuntary movements (AIMs), comparing continuous and pulsatile administration of rotigotine with pulsatile administration of 3,4-dihydroxy-l-phenylalanine (l-DOPA) for reference. Rats were unilaterally lesioned with 6 hydroxydopamine (6-OHDA). For pulsatile administration, l-DOPA-methylester (10 mg/kg l-DOPA i.p.) or rotigotine (1 mg/kg i.p.) were administered once or twice daily. For continuous administration, a slow release formulation of rotigotine was injected s.c. at a dose of 1 mg/kg every 48 h (experiment I) or every 24 h (experiment II). Pulsatile administration of rotigotine and l-DOPA caused contraversive rotations increasing progressively upon each successive treatment. AIMs started to occur after the second administration of l-DOPA but hardly after pulsatile rotigotine. Continuous rotigotine increased rotations, which reached a plateau after the second administration. No AIMs were observed under continuous administration. The continuous administration of rotigotine did not induce sensitization or AIMs, suggesting that continuous stimulation of dopaminergic receptors by rotigotine has no propensity to induce dyskinesia in this experimental model.

Keywords

Parkinson’s disease Therapy Continuous Pulsatile dopaminergic stimulation Abnormal involuntary movements Dyskinesia Rotational activity Rotigotine l-DOPA Sensitization 

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Werner J. Schmidt
    • 1
  • Heike Lebsanft
    • 1
  • Manfred Heindl
    • 1
  • Manfred Gerlach
    • 2
  • Edna Gruenblatt
    • 3
  • Peter Riederer
    • 2
  • Andreas Mayerhofer
    • 1
  • Dieter K. A. Scheller
    • 4
  1. 1.Zoologisches Institut der Universitaet Tuebingen, Abt. NeuropharmakologieTuebingenGermany
  2. 2.Klinik fuer Kinder und JugendpsychiatriePsychosomatik und Psychotherapie der Universitaet Wuerzburg, Labor für klinische NeurobiologieWuerzburgGermany
  3. 3.Klinik fuer PsychiatriePsychosomatik und Psychotherapie der Universitaet Wuerzburg, Abt. Klinische NeurochemieWuerzburgGermany
  4. 4.UCB Pharma S.A. CNS Research, Department Pharmacology of Parkinson’s Disease and Movement DisordersChemin du ForiestBraine l’AlleudBelgium