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

Molecular Neurodegeneration

António J Salgado¹  Nuno Sousa¹  Ana J Rodrigues¹  Rui Lima¹  Carla Rodrigues¹  José M Pêgo¹  Bárbara Coimbra¹  Filipa L Campos¹  Miguel M Carvalho¹ 

[1]ICVS/3B’s, PT Government Associate Laboratory, Braga/Guimarães, Portugal

关键词: Paroxetine;    Bupropion;    Levodopa;    Emotion;    Motor behavior;    6-OHDA;    Parkinson’s disease;   

Others  :  863269
DOI  :  10.1186/1750-1326-8-14

 received in 2013-01-29, accepted in 2013-04-12,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Carvalho et al.; licensee BioMed Central Ltd.

【 图 表 】

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