Study of basal ganglia nuclei in a rat model of dyskinesia

• Autores: Asier Aristieta Arbelaiz
• Directores de la Tesis: José Ángel Ruiz Ortega (dir. tes.), Luisa Ugedo Urruela (dir. tes.)
• Lectura: En la Universidad del País Vasco - Euskal Herriko Unibertsitatea ( España ) en 2012
• Idioma: español
• Tribunal Calificador de la Tesis: Pedro Rolando Grandes Moreno (presid.), Rosa María Hernández Martín (secret.), Liliana García Rodríguez (voc.), Rosario Moratalla Villalba (voc.), Laura Lambas Señas (voc.)
• Materias:
  • Ciencias médicas
    • Medicina interna
    • Farmacodinámica
    • Farmacología
• Texto completo no disponible (Saber más ...)
• Resumen

  • The treatment of Parkinson¿s disease (PD) with L-DOPA induces abnormal involuntary movements known as L-DOPA-induced dyskinesia (LID) in the majority of PD patients. The aim of this study was to investigate the role of the subthalamic nucleus (STN) in the etiopathology of LID and in the movement disorders related to selective 5-HT reuptake inhibitors. As well as the relationship of the STN with the basal ganglia output nuclei (the entopeduncular nucleus, EP and the substantia nigra pars reticulata, SNr). To achieve these objectives we used single-unit extracellular recording, behavioural and molecular approaches in hemi-parkinsonian rats rendered dyskinetic by chronic L-DOPA administration.Our results show that the treatment with L-DOPA does not modifies the hyperactivity of STN neurons observed in 6-OHDA lesioned rats. However, the lesion of the STN modestly reduces the LID and tends to normalize the striatal molecular changes associated with LID. In this dyskinetic rat model, the chronic L-DOPA treatment induces electrophysiological changes in the EP nucleus and the SNr, showing a hyperactivity pattern. These modifications are partially reversed by the acute L-DOPA challenge. Additionally, in dyskinetic animals the activity of STN neurons correlates with the activity of EP nucleus and SNr neurons. Moreover, STN neurons electrical activity is altered after the modulation of the serotonergic system. All together, this study provides further information of the role of the STN in LID and its relation with the basal ganglia output nuclei. We also give evidences for the serotonergic regulation of STN neuron activity.