British journal of pharmacology · 2016
The acute and long-term L-DOPA effects are independent from changes in the activity of dorsal raphe serotonergic neurons in 6-OHDA lesioned rats.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Miguelez C, Navailles S, De Deurwaerdère P, Ugedo L
Аннотация
BACKGROUND AND PURPOSE: L-DOPA is still the most efficacious pharmacological treatment for Parkinson's disease. However, in the majority of patients receiving long-term therapy with L-DOPA, its efficacy is compromised by motor complications, notably L-DOPA-induced dyskinesia. Evidence suggests that the serotonergic system is involved in the therapeutic and the side effects of L-DOPA. Here, we investigate if long-term L-DOPA treatment alters the activity of the dorsal raphe nucleus (DRN) and its responses to serotonergic drugs.
EXPERIMENTAL APPROACH: We measured the responses of serotonergic neurons to acute and chronic L-DOPA treatment using in vivo electrophysiological single unit-extracellular recordings in the 6-OHDA-lesion rat model of Parkinson's disease.
KEY RESULTS: The results showed that neither acute nor chronic L-DOPA administration (6 mg·kg(-1) s.c.) altered the properties of serotonergic-like neurons. Furthermore, no correlation was found between the activity of these neurons and the magnitude of L-DOPA-induced dyskinesia. In dyskinetic rats, the inhibitory response induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.0625-16 μg·kg(-1) , i.v.) was preserved. Nonetheless, L-DOPA impaired the ability of the serotonin reuptake inhibitor fluoxetine (0.125-8 mg·kg(-1) , i.v) to inhibit DRN neuron firing rate in dyskinetic animals.
CONCLUSIONS AND IMPLICATIONS: Although serotonergic neurons are involved in the dopaminergic effects of L-DOPA, we provide evidence that the effect of L-DOPA is not related to changes of the activity of DRN neurons. Rather, L-DOPA might reduce the efficacy of drugs that normally enhance the extracellular levels of serotonin.
LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.
EXPERIMENTAL APPROACH: We measured the responses of serotonergic neurons to acute and chronic L-DOPA treatment using in vivo electrophysiological single unit-extracellular recordings in the 6-OHDA-lesion rat model of Parkinson's disease.
KEY RESULTS: The results showed that neither acute nor chronic L-DOPA administration (6 mg·kg(-1) s.c.) altered the properties of serotonergic-like neurons. Furthermore, no correlation was found between the activity of these neurons and the magnitude of L-DOPA-induced dyskinesia. In dyskinetic rats, the inhibitory response induced by the 5-HT1A receptor agonist 8-OH-DPAT (0.0625-16 μg·kg(-1) , i.v.) was preserved. Nonetheless, L-DOPA impaired the ability of the serotonin reuptake inhibitor fluoxetine (0.125-8 mg·kg(-1) , i.v) to inhibit DRN neuron firing rate in dyskinetic animals.
CONCLUSIONS AND IMPLICATIONS: Although serotonergic neurons are involved in the dopaminergic effects of L-DOPA, we provide evidence that the effect of L-DOPA is not related to changes of the activity of DRN neurons. Rather, L-DOPA might reduce the efficacy of drugs that normally enhance the extracellular levels of serotonin.
LINKED ARTICLES: This article is part of a themed section on Updating Neuropathology and Neuropharmacology of Monoaminergic Systems. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.13/issuetoc.