title: 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.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Spain.|Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Miguelez
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.
authors.forename: S
authors.initials: S
authors.lastname: Navailles
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France.
authors.forename: P
authors.initials: P
authors.lastname: De Deurwaerdère
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), Leioa, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Ugedo
mesh_terms: D000818:Animals; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology*; D065847:Dorsal Raphe Nucleus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000473:pathology; D007980:Levodopa / Q000008:administration & dosage / Q000494:pharmacology*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D012701:Serotonin; D007980:Levodopa; D016627:Oxidopamine