The relationship between the location of a lesion in the striatal dopaminergic innervation and its behavioral manifestation in a 6-hydroxydopamine-induced model of Parkinson's disease in rats

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Abstract

Introduction. Animal modelling of Parkinson’s disease is an essential step in studying disease pathogenesis and searching for effective treatment methods. An accurate assessment of the resulting model is critical.

The aim of the study was to identify the correlation between the location of a lesion in the striatal dopaminergic innervation when the neurotoxin 6-hydroxydopamine (6-OHDA) was administered to rodents and the resulting behavior.

Materials and methods. The study was carried out on 75 male Wistar rats that received intranigral injection of 3 µl of 6-OHDA at a dose of 4 µg/µl. The animals were examined in the open field test and narrowing beam walking test 33 days after administration, after which some of the animals were decapitated (n = 25) for immunohistochemical analysis.

Results. The inactive animal group was statistically significantly different from the active animal group, with more pronounced damage to the dopamine endings in the dorsomedial (p = 0.0235) and ventral (p = 0.091) striatum. In contrast, in the active animals, the lesion was primarily in the dorsolateral striatum. In the inactive animal group, the mean distance travelled in the open field test was significantly shorter (p < 0.001), while freezing time (p < 0.0168) and the average score on the neuroticism scale (p < 0.001) were higher compared to the active animals. Spearman's correlation results showed a significant negative correlation (rS = –0.762; p < 0.0001) between tyrosine hydroxylase staining intensity in the dorsolateral striatum and freezing time in the open field test. No correlation was found between freezing time and damage to other striatal areas.

Conclusion. Damage to the dorsomedial and dorsolateral striatum causes less severe motor and emotional disturbances than damage to the ventral striatum. The narrowing beam walking test can be used to assess the presence and severity of striatal damage reliably. This evaluation is critical in studies of subsequent treatment efficacy to reduce Parkinsonian syndrome.

About the authors

Alla V. Stavrovskaya

Research Center of Neurology

Author for correspondence.
Email: alla_stav@mail.ru
Russian Federation, Moscow

Dmitry N. Voronkov

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

Artem S. Olshansky

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

Anastasia S. Gushchina

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

Nina G. Yamshikova

Research Center of Neurology

Email: alla_stav@mail.ru
Russian Federation, Moscow

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Copyright (c) 2021 Stavrovskaya A.V., Voronkov D.N., Olshansky A.S., Gushchina A.S., Yamshikova N.G.

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