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

C Miguelez, S Navailles, P De Deurwaerdère, L Ugedo
British Journal of Pharmacology. 2016-03-08; 173(13): 2135-2146
DOI: 10.1111/bph.13447

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Miguelez C(1)(2), Navailles S(3)(4), De Deurwaerdère P(3)(4), Ugedo L(1).

Author information:
(1)Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Spain.
(2)Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
(3)Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.
(4)CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.

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

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

© 2016 The Authors. British Journal of Pharmacology published by John Wiley &
Sons Ltd on behalf of British Pharmacological Society.


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