Behavioral characterization of the 6-hydroxidopamine model of Parkinson's disease and pharmacological rescuing of non-motor deficits

BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative condition that is characterized by motor symptoms as a result of dopaminergic degeneration, particularly in the mesostriatal pathway. However, in recent years, a greater number of clinical studies have focused on the emergence of non-motor symptoms in PD patients, as a consequence of damage on the mesolimbic and mesocortical dopaminergic networks, and on their significant impact on the quality of life of PD patients. Herein, we performed a thorough behavioral analysis including motor, emotional and cognitive dimensions, of the unilateral medial forebrain bundle (MFB) 6-hydroxidopamine (6-OHDA)-lesioned model of PD, and further addressed the impact of pharmacological interventions with levodopa and antidepressants on mood dimensions. RESULTS: Based on apomorphine-induced turning behaviour and degree of dopaminergic degeneration, animals submitted to MFB lesions were subdivided in complete and incomplete lesion groups. Importantly, this division also translated into a different severity of motor and exploratory impairments and depressive-like symptoms; in contrast, no deficits in anxiety-like and cognitive behaviors were found in MFB-lesioned animals. Subsequently, we found that the exploratory and the anhedonic behavioural alterations of MFB-lesioned rats can be partially improved with the administration of both levodopa or the antidepressant bupropion, but not paroxetine. CONCLUSIONS: Our results suggest that this model is a relevant tool to study the pathophysiology of motor and non-motor symptoms of PD. In addition, the present data shows that pharmacological interventions modulating dopaminergic transmission are also relevant to revert the non-motor behavioral deficits found in the disease.We would like to acknowledge the funds attributed by Fundacao Calouste de Gulbenkian to A.J. Salgado under the scope of the The Gulbenkian Program to Support Research in the Life Sciences, and Portuguese Foundation for Science and Technology: Ciencia 2007 Program to A.J. Salgado; the PhD scholarships to M. M. Carvalho (SFRH/BD/51061/2010) and F. L. Campos (SFRH/BD/47311/2008), and the Post-Doctoral Fellowship to A.J. Rodrigues (SFRH/BPD/33611/2009) We want to further acknowledge Carina Cunha, Fabio Teixeira, Joao Bessa and Joao Cerqueira for their contribution to this work