Swim-test as a function of motor impairment in MPTP model of Parkinson's disease: a comparative study in two mouse strains.
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.
Haobam
Reena
R
Division of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology, Calcutta, India.
Sindhu
Kizhakke M
KM
Chandra
Goutam
G
Mohanakumar
Kochupurackal P
KP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D001522:Behavior, Animal; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D016472:Motor Neuron Disease / Q000209:etiology* / Q000378:metabolism; D009069:Movement Disorders / Q000209:etiology; D010300:Parkinson Disease / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D013223:Statistics as Topic; D013550:Swimming; D014202:Tremor / Q000209:etiology
D015259:Dopamine Agents; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine