V-113 | Dopaminergic agonist-induced structural remodeling of striatal neurons and its correlation with abnormal involuntary movements in parkinsonian animals

Neurochemistry and Neuropharmacology
Author: Liliana Teresita Tribbia | Email: teresita.tribbia@uner.edu.ar

Liliana T. Tribbia^1°, Félix Fares Taie^2°3°,Lorena Rela^2°3°, Juan E. Belforte^2°3°, M. Gustavo Murer^2°3°, Oscar S. Gershanik^4°, Irene R. E. Taravini^1°

^1° Laboratorio de Neurobiología Experimental. LNE – ICTAER – UNER – CONICET, Gualeguaychú, Entre Ríos, Argentina.
^2° Universidad de Buenos Aires, Facultad de Medicina, Departamento de Ciencias Fisiológicas, Grupo de Neurociencia de Sistemas, Ciudad de Buenos Aires, Argentina.
^3° CONICET, Universidad de Buenos Aires, Instituto de Fisiología y Biofísica Bernardo Houssay (IFIBIO Houssay), Buenos Aires, Argentina.
^4° Consultor Emérito Laboratorio de Neurobiología Experimental, LNE-ICTAER-UNER-CONICET, Gualeguaychú, Entre Ríos, Argentina.

L-DOPA-induced dyskinesia (LID), is a difficult adverse effect associated with Parkinson’s disease treatment, often leading to significant disability. LID is associated with the occurrence of structural plasticity in striatal medium spiny neurons (MSNs) dendritic spines. However, it remains unclear whether the administration of selective D1R or D2R agonists induces similar structural modulation, potentially contributing to abnormal involuntary movement (AIM) development. We propose to determine whether MSNs undergo structural plastic changes after the development of AIM by chronic treatment with selective dopaminergic agonists in animals with severe damage to the nigrostriatal dopaminergic pathway. D1-tomato transgenic mice lesioned with a unilateral injection of 6-OHDA or vehicle (SHAM control group) were treated with SKF-38393 (D1/D5 agonist, 2 mg/kg), QUINPIROLE (D2-type receptor agonist, 0.5 mg/kg) or vehicle for 15 days. Axial, limb and orofacial AIM were scored using a validated rating scale. Lesioned mice treated with both selective dopaminergic agonists developed forelimb, axial and orofacial AIM, which correlated with an increase in the striatal expression of FosB, a synaptic plasticity marker. Control animals did not show AIM, but displayed vacuous chewing movements under the effect of dopaminergic agonists. Studies are in course to determine whether AIM induced by selective agonists relate to changes in striatal synaptic microarchitecture, as is the case with LID.