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New insights into the range of behaviors induced by the dopamine D1 agonist SKF-38393 in normal and hemiparkinsonian mice

Liliana Teresita Tribbia

  • Gualeguaychú,
  • Argentina
  • Liliana T. Tribbia ¹
  • , Juan E. Belforte ²
  • , Gustavo Murer ²
  • , Oscar S. Gershanik ³
  • , Irene R.E. Taravini ¹
  • 1 Laboratorio de Neurobiología Experimental. LNE-FBRO-UNER, Gualeguaychú, Entre Ríos, Argentina.
  • 2 Grupo Neurociencia de Sistemas, IFIBIO-Houssay, UBA-CONICET, Ciudad de Buenos Aires, Argentina.
  • 3 Consultor Emérito Laboratorio de Neurobiología de la Enfermedad de Parkinson y Laboratorio de Neurobiología Experimental, Universidad de Buenos Aires, Universidad de Nacional de Entre Ríos y CONICET.

Parkinson’s disease is the second most prevalent neurodegenerative disease worldwide. The degenerative process primarily affects dopaminergic neurons of the substantia nigra pars compacta, which innervates the striatum through the nigrostriatal pathway. Medium spiny neurons comprise more than 90% of the neurons in the striatum and are organized into two GABAergic projection systems: striatonigral pathway, expressing D1-type dopamine receptors (D1R) and striatopallidal pathway, expressing D2R. The stimulation of D1R by selective agonists (like SKF-38393) participates directly in the development and manifestation of abnormal involuntary movements (AIMs). However, no scoring systems exist to evaluate the multiple components of SKF-38393-induced stereotypy in normal and hemiparkinsonian mice. Therefore, we propose to improve the behavioral measurement parameters related to the stereotypies and movements of these mice in order to better understand the behavioral properties of this dopamine agonist. C57BL/6J mice lesioned by 6-OHDA injection into MFB and control mice were treated with increasing doses of SKF-38393 (0.5-1-2mg/kg/day) or distilled water (VEH) for 15 days. The experimental groups were 6-OHDA/SKF, 6-OHDA/VEH, control/SKF and control/VEH. We have designed a new scoring scale for AIMs based on careful observation of each experimental subject and were able to recognize and rate a broad spectrum of behaviors related to SKF treatment.