title: L-DOPA elicits non-vesicular releases of serotonin and dopamine in hemiparkinsonian rats in vivo.
abstract: The control of the secretory activity of serotonergic neurons has been pointed out to reduce motor and non-motor side effects of the antiparkinsonian drug L-DOPA. This strategy deserves further investigation because it is presently unclear whether L-DOPA promotes a non-vesicular release of dopamine and serotonin from serotonergic neurons. To get a full neurochemical picture compatible with the existence of such a mechanism, we combined multisite intracerebral microdialysis, post mortem tissue measurement and single unit extracellular recordings in the dorsal raphe nucleus from hemiparkinsonian rats. L-DOPA (3-100mg/kg, ip.) non-homogeneously decreased extracellular serotonin levels in the striatum, substantia nigra pars reticulata, hippocampus and prefrontal cortex and homogenously serotonin tissue content in the striatum, cortex and cerebellum. L-DOPA (12mg/kg) did not modify the firing rate or pattern of serotonergic-like neurons recorded in the dorsal raphe nucleus. When focusing on serotonin release in the prefrontal cortex and the hippocampus, we found that L-DOPA (12 or 100mg/kg) enhanced serotonin extracellular levels in both regions upon Ca(2+) removal. Concomitantly, L-DOPA-stimulated dopamine release partly persisted in the absence of Ca(2+) in a region-dependent manner. Local application of the serotonin reuptake inhibitor citalopram (1µM) blunted the responses to L-DOPA (3-12mg/kg), measured as extracellular dopamine levels, most prominently in the hippocampus. These data stress that L-DOPA, already at low to moderate doses, promotes non-vesicular releases of serotonin and dopamine in a region-dependent manner.
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain; Department of Pharmacology, Faculty of Pharmacy, University of the Basque Country (UPV/EHU), 01006 Vitoria-Gasteiz, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Miguelez
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Navailles
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Delaville
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Loïse
authors.initials: L
authors.lastname: Marquis
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Lagière
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
authors.forename: Abdelhamid
authors.initials: A
authors.lastname: Benazzouz
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
authors.forename: Luisa
authors.initials: L
authors.lastname: Ugedo
authors.affiliation: Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. Electronic address: deurwaer@u-bordeaux2.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: De Deurwaerdère
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002777:Cholestanols; D015283:Citalopram / Q000494:pharmacology; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009928:Organ Specificity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D059010:Single-Cell Analysis; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000978:Antiparkinson Agents; D002777:Cholestanols; D015283:Citalopram; D015259:Dopamine Agents; D006897:Hydroxyindoleacetic Acid; D007980:Levodopa; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C000602165:microdiplane
keywords: Electrophysiology; Exocytosis; Hippocampus; Intracerebral microdialysis; Prefrontal cortex; Tissue measurement