Pole test is a useful method for evaluating the mouse movement disorder caused by striatal dopamine depletion

doi:10.1016/S0165-0270(96)02211-X

Journal of Neuroscience Methods

Volume 73, Issue 1, 25 April 1997, Pages 45-48

https://doi.org/10.1016/S0165-0270(96)02211-X Get rights and content

Abstract

We evaluated the behavioral recovery of mice with 6-hydroxydopamine (6-OHDA)-induced lesions using a pole test. T_LA (locomotor activity time) 1, 2, and 3 days after intracerebroventricular 6-OHDA injection (T_LA(1-3D)) was correlated significantly with the levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the striatum 7 days after the injection of 6-OHDA, but 5-hydroxyindoleacetic acid (5-HIAA) and serotonin (5-HT) had no correlation with T_LA(1-3D). The mice whose T_LA(1-3D) was more than the median showed about 60% depletion of striatal DA and increased DA turnover, and recovered from movement disorders 4 days after injection. These results show that presynaptic neuroadaptations and behavioral recovery exist in this animal model. Thus, the pole test appears to be useful in predicting the extent of the lesion to select a mouse in which the receptive fields of the dopaminergic cells are denervated.

Introduction

Parkinson's disease (PD) is a chronic, progressive, neurodegenerative disorder characterized by resting tremor, rigidity, stooped posture, bradykinesia and akinesia or hypokinesia. In rats with unilateral 6-hydroxydopamine (6-OHDA) injection along the nigrostriatal pathway, degeneration of the dopaminergic neurons does not result in motor behavior impairment until 80–90% of neurons are lost (Zigmond and Stricker, 1984), and the animals gradually recover from such movement disorders if destruction of the nigrostriatal dopamine system is less than 95% (Robinson et al., 1994a). This behavioral recovery depends on presynaptic and postsynaptic adaptations (Marshall, 1979; Neve et al., 1982; Robinson and Whishaw, 1988; Altar et al., 1989; Robinson et al., 1994a, Robinson et al., 1994b). In rats, the apomorphine or amphetamine rotation test is commonly used to assess the degree of striatal DA denervation (Hudson et al., 1993; Robinson et al., 1994b). In mice, a pole test is used to assess the effects of an injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (Ogawa et al., 1985, Ogawa et al., 1987; Tasaki et al., 1991), which is commonly used as a model of Parkinson's disease (Arai et al., 1990). When the pole test is performed, the mouse is placed head-upward on the top of a rough-surfaced vertical pole and the time until it descends to the floor is recorded to assess the mouse locomotor activity. The purpose of this study was to investigate the ability of the pole test to predict the extent of the lesion in 6-OHDA-lesioned mice for the purpose of selecting a mouse in which the receptive fields of the dopaminergic cells are denervated.

Section snippets

Materials and methods

Male ICR mice weighing 30–35 g (Charles River Japan, Kanagawa, Japan) at the beginning of the experiments were used (n=47). The animals were housed in a temperature-controlled room with a 12-h light/dark cycle and were given free access to food and water. Intracerebroventricular injection of 2 μl of 6-OHDA solution [Funakoshi, Japan; 40 mg/ml, in physiological saline containing 0.1% ascorbic acid (SA)] (n=34) or SA (n=13) were performed under light ether anesthesia (Ogawa et al., 1994). All

Results

The correlation coefficient between T_LA(1-3D) and striatal amine concentrations and turnover are shown in Table 1. DA, DOPAC and HVA had a significant negative correlation with T_LA(1-3D), and HVA/DA and (DOPAC+HVA)/DA had a significant positive correlation with T_LA(1-3D), though 5-HIAA, 5-HT and DOPAC/DA had no correlation with T_LA(1-3D).

The correlation between DA and T_LA(1-3D) is shown in Fig. 1. The mice were divided into two groups: those whose T_LA(1-3D) was more than median (T_LA(1-3D)

Discussion

The major conclusion to be drawn from this study is that DA, DOPAC and HVA in the ST 7 days after the injection of 6-OHDA were significantly correlated with T_LA(1-3D). Although T_LA(1-3D) may vary according to the experimental condition, for example surface roughness, diameter and height of the pole, this result suggests that T_LA(1-3D) is useful for predicting the extent of DA depletion in the ST. Since tissue DA levels are known to be a good index of the degree of striatal DA denervation after

Acknowledgements

This work was supported in part by Grants-in-Aid for Scientific Research from the Japanese Ministry of Education, Science, Sports and Culture, and by a Grant-in-Aid from the Research Committee on CNS degenerative diseases of the Japanese Ministry of Health and Welfare.

References (15)

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