Swim-test as a function of motor impairment in MPTP model of Parkinson's disease: a comparative study in two mouse strains

Behav Brain Res. 2005 Sep 8;163(2):159-67. doi: 10.1016/j.bbr.2005.04.011.

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease that exhibits motor dysfunctions, such as tremor, akinesia and rigidity. In the present study, we investigated whether swim-test could be used as one of the behavioural monitoring techniques to study motor disability in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in two mouse strains, Balb/c and C57BL/6. Mice were treated with different doses of MPTP (10, 20 and 30 mg/kg, twice, 16 h apart), and were subjected to swim-test on the third day of the first MPTP injection. MPTP-induced tremor was monitored at 30 min, and akinesia and rigidity developed were studied 3 h after the second MPTP treatment. While tremor and akinesia produced were dose-dependent and the intensity of tremor was comparable in the two strains of mice studied, the latter response in C57BL/6 was significantly lesser than that observed in Balb/c. Rigidity exhibited in Balb/c mice were dose-dependent, but not in C57BL/6. There was observed an inverse relationship between swim-score and the doses of MPTP in both the strains. MPTP caused a significant and dose-dependent reduction in striatal dopamine level in both the strains of mice, when assayed on the fourth day employing an HPLC with electrochemical detector. A significant positive correlation existed (r = 0.94 for Balb/c and r = 0.82 for C57BL/6) for the striatal dopamine-depletion and the swim-score in the MPTP-treated mice. While swim deficit and striatal dopamine loss were long lasting (till the third week) in C57BL/6, in Balb/c mice the motor deficit showed recovery by the second week. In these animals, a significant attenuation in striatal dopamine loss was observed by the third week. These results indicate that swim ability is directly proportional to striatal dopamine content, and suggest that swim-test could be used as a major technique to monitor motor dysfunction in experimental animals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / administration & dosage
  • Animals
  • Behavior, Animal
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine / metabolism
  • Dopamine Agents / administration & dosage
  • Dose-Response Relationship, Drug
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Neuron Disease / etiology*
  • Motor Neuron Disease / metabolism
  • Movement Disorders / etiology
  • Parkinson Disease / physiopathology*
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / physiopathology*
  • Serotonin / metabolism
  • Species Specificity
  • Statistics as Topic
  • Swimming*
  • Tremor / etiology

Substances

  • Dopamine Agents
  • Serotonin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Dopamine