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

Mol Neurodegener. 2013 Apr 26:8:14. doi: 10.1186/1750-1326-8-14.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Agents / pharmacology
  • Animals
  • Antidepressive Agents / pharmacology
  • Antiparkinson Agents / pharmacology*
  • Behavior, Animal / drug effects*
  • Bupropion / pharmacology
  • Disease Models, Animal
  • Immunohistochemistry
  • Levodopa / pharmacology
  • Mood Disorders / etiology*
  • Motor Activity / drug effects
  • Oxidopamine / toxicity
  • Parkinsonian Disorders / complications*
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / psychology*
  • Paroxetine / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Adrenergic Agents
  • Antidepressive Agents
  • Antiparkinson Agents
  • Bupropion
  • Paroxetine
  • Levodopa
  • Oxidopamine