L-DOPA elicits non-vesicular releases of serotonin and dopamine in hemiparkinsonian rats in vivo

Cristina Miguelez, Sylvia Navailles, Claire Delaville, Loïse Marquis, Mélanie Lagière, Abdelhamid Benazzouz, Luisa Ugedo, Philippe De Deurwaerdère
European Neuropsychopharmacology. 2016-08-01; 26(8): 1297-1309
DOI: 10.1016/j.euroneuro.2016.05.004

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Miguelez C(1), Navailles S(2), Delaville C(2), Marquis L(2), Lagière M(2), Benazzouz A(2), Ugedo L(3), De Deurwaerdère P(4).

Author information:
(1)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.
(2)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France.
(3)Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country (UPV/EHU), 48940 Leioa, Spain.
(4)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France; CNRS, Institut des Maladies Neurodégénératives, UMR 5293, F-33000 Bordeaux, France. E

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.

 

Auteurs Bordeaux Neurocampus