title: Behavioral characterization of the 6-hydroxidopamine model of Parkinson's disease and pharmacological rescuing of non-motor deficits.
abstract: 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.
authors.affiliation: Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus de Gualtar, Braga, Portugal.
authors.forename: Miguel M
authors.initials: MM
authors.lastname: Carvalho
authors.forename: Filipa L
authors.initials: FL
authors.lastname: Campos
authors.forename: Bárbara
authors.initials: B
authors.lastname: Coimbra
authors.forename: José M
authors.initials: JM
authors.lastname: Pêgo
authors.forename: Carla
authors.initials: C
authors.lastname: Rodrigues
authors.forename: Rui
authors.initials: R
authors.lastname: Lima
authors.forename: Ana J
authors.initials: AJ
authors.lastname: Rodrigues
authors.forename: Nuno
authors.initials: N
authors.lastname: Sousa
authors.forename: António J
authors.initials: AJ
authors.lastname: Salgado
mesh_terms: D018663:Adrenergic Agents / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D016642:Bupropion / Q000494:pharmacology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology; D019964:Mood Disorders / Q000209:etiology*; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000150:complications* / Q000473:pathology / Q000523:psychology*; D017374:Paroxetine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018663:Adrenergic Agents; D000928:Antidepressive Agents; D000978:Antiparkinson Agents; D016642:Bupropion; D017374:Paroxetine; D007980:Levodopa; D016627:Oxidopamine