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

• Published in: Behavioural brain research Vol. 163; no. 2; pp. 159 - 167
• Main Authors: Haobam, Reena, Sindhu, Kizhakke M., Chandra, Goutam, Mohanakumar, Kochupurackal P.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 08-09-2005; Elsevier Science
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - administration & dosage; Adult and adolescent clinical studies; Akinesia; Animals; Behavior, Animal; Biological and medical sciences; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine - metabolism; Dopamine Agents - administration & dosage; Dopamine loss and behaviour; Dose-Response Relationship, Drug; Freezing Reaction, Cataleptic - drug effects; Freezing Reaction, Cataleptic - physiology; Male; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Motor Activity - drug effects; Motor Neuron Disease - etiology; Motor Neuron Disease - metabolism; Movement Disorders - etiology; Neurology; Organic mental disorders. Neuropsychology; Parkinson Disease - physiopathology; Parkinsonian Disorders - metabolism; Parkinsonian Disorders - physiopathology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rigidity; Serotonin - metabolism; Species Specificity; Statistics as Topic; Strain difference; Susceptibility to MPTP; Swimming; Tremor - etiology; Strain difference; Susceptibility to MPTP; Rigidity; Dopamine loss and behaviour; Akinesia; Animal model; Motor system disorder; Parkinson disease; Mus domesticus; Degenerative disease; Behavior; Neurological disorder; Nervous system diseases; Dopamine; Rodentia; Catecholamine; Cerebral disorder; Strain; Toxin; Vertebrata; Sensitivity; Mammalia; Central nervous system disease; Neurotoxin; Neurotransmitter; Comparative study; Extrapyramidal syndrome
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2005.04.011

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.