Abstract
Rationale: Treatment of Parkinson's disease has been by now symptomatic. The literature on the efficacy and side effects of levodopa has been contradictory. Some authors mention an anti-depressant effect of the agent, while others believe that it is exactly levodopa that eventually induces the occurrence of depressive symptoms.Aim: To reproduce the OHDA-hemiparkinsonism rat model with subsequent assessment of both external and structural manifestations of the disorder, as well as to study the efficacy of levodopa for motor and non-motor symptoms of parkinsonism.Materials and methods: The study was performed in 52 male Wistar rats. The disease model included stereotaxic administration of neurotoxic 6-OHDA into the pars compacta of the substantia nigra. At 2 months after the administration, the animals underwent test for motor (Rotarod, cylinder, ketamine-induced rotation in the rotometer) and non-motor abnormalities (open field, social interest, conditioned escape response).Results: In 18% of the animals no hemiparkinsonism symptoms were found. 32% of rats had only motor symptoms, whereas in 50% of the animals both motor and non-motor symptoms were noted. Levodopa could partially correct the motor abnormalities, with augmentation of depressive-like behavior.Conclusion: Levodopa has shown its partial efficacy in correction of the motor symptoms caused by administration of 6-OHDA neurotoxin; however, it caused such side effects as augmentation of depressive-like behavior and anxiety.
Highlights
Low BDNF is associated with cognitive impairments in patients with Parkinson's disease
All the authors made their significant contributions to the research and preparation of the article, have read and approved the final version before submission
Summary
Продепрессивный эффект леводопы в модели 6-OHDA-индуцированного гемипаркинсонизма у крыс. Цель – воспроизведение модели OHDA-гемипаркинсонизма у крыс с последующим исследованием как внешних, так и структурных проявлений патологии, а также изучение эффективности леводопы в направлении нивелирования моторных и немоторных проявлений симптомов паркинсонизма. Ключевые слова: нейродегенеративные заболевания, болезнь Паркинсона, 6-OHDA, леводопа. Этиология болезни Паркинсона остается дискутабельной, лечение направлено на устранение или уменьшение проявлений моторных симптомов. Длительное время исследования болезни Паркинсона акцентировались только на моторных симптомах. К признакам депрессии при болезни Паркинсона относят раздражительность, недостаток энергии, нерешительность, печаль, ангедонию и другие, при этом данные симптомы часто недооцениваются самими больными [7, 8]. Препарат леводопы – золотой стандарт лечения болезни Паркинсона – впервые успешно применен в 1960-х гг., однако при длительной терапии отмечается снижение ее эффективности и развитие инвалидизирующих моторных осложнений [15, 16]. Целью нашего исследования стала экспериментальная проверка противоречивых данных о побочных действиях леводопы на немоторную симптоматику в модели гемипаркинсонизма у крыс
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