Behavioural Brain Research 163 (2005) 159–167 Research report Swim-test as a function of motor impairment in MPTP model of Parkinson’s disease: A comparative study in two mouse strains Reena Haobam, Kizhakke M. Sindhu, Goutam Chandra, Kochupurackal P. Mohanakumar ∗ Division of Clinical & Experimental Neuroscience, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Calcutta 700032, India Received 10 December 2004; received in revised form 25 April 2005; accepted 25 April 2005 Available online 6 June 2005 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. © 2005 Elsevier B.V. All rights reserved. Keywords: Dopamine loss and behaviour; Susceptibility to MPTP; Akinesia; Rigidity; Strain difference 1. Introduction Symptoms of Parkinson’s disease (PD) include several movement abnormalities, such as tremor, rigidity, bradykine- sia (slowness of voluntary movements), akinesia (difficulty in initiating movement), masked face and gait and posture abnormalities. The pathology of idiopathic PD is attributed to ∗ Corresponding author. Tel.: +91 33 2413 3223 (O); fax: +91 33 2473 5197/72 3967. E-mail address: mohankumar@iicb.res.in (K.P. Mohanakumar). the progressive loss of dopaminergic neurons from the sub- stantia nigra (SN) region of the brain. The potent parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), causes PD in animals and is one of the most accepted models, reproducing several of the symptoms of the disease along with specific and copious degeneration of SN neurons [3]. Humans [8] and many other animal species including non-human primates [24], guinea pigs [25], mice [1,43] and cats [35] are susceptible to this neurotoxin. While humans and primates display overt behavioural abnormalities, none of the laboratory animals exhibit such behavioural dys- 0166-4328/$ – see front matter © 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.bbr.2005.04.011