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Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA

dc.contributor.authorGantz, Stephanie C.
dc.contributor.authorLevitt, Erica S.
dc.contributor.authorLlamosas Muñozguren, Nerea ORCID
dc.contributor.authorNeve, Kim A.
dc.contributor.authorWilliams, John T.
dc.date.accessioned2016-04-07T10:30:44Z
dc.date.available2016-04-07T10:30:44Z
dc.date.issued2015-08-11
dc.identifier.citationCell Reports 12(6) : 944-954 (2014)es
dc.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/10810/17824
dc.description.abstractImbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson's disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2-receptor-mediated inhibitory postsynaptic current (IPSC) in dopamine neurons of the substantia nigra. This augmentation was largely due to dopamine release from 5-HT terminals. Selective optogenetic stimulation of 5-HT terminals evoked dopamine release, producing D2-receptor-mediated IPSCs following treatment with L-DOPA. In the dorsal raphe, L-DOPA produced a long-lasting depression of the 5-HT1A-receptor-mediated IPSC in 5-HT neurons. When D2 receptors were expressed in the dorsal raphe, application of L-DOPA resulted in a D2-receptor-mediated IPSC. Thus, treatment with L-DOPA caused ectopic dopamine release from 5-HT terminals and a loss of 5-HT-mediated synaptic transmission.es
dc.description.sponsorshipThis work was supported by NIH DA04523 and DA034388 (J.T.W.) and by Merit Review Award BX000810 from the US Department of Veterans Affairs Biomedical Laboratory Research and Development (K.A.N.). We thank Drs. Tianyi Mao and Mark Pennesi for supplying Ai9 and Ai32 mice, and 5-HT1B receptor KO mice, respectively, and Maozhen Qin for help with mouse husbandry.es
dc.language.isoenges
dc.publisherCell Presses
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.subjectrat substantia-nigraes
dc.subjectdorsal raphe nucleuses
dc.subjectparinsons-diseasees
dc.subjectcerbrospinal-fluides
dc.subjectinduced dyskinesiaes
dc.subjectamino-acides
dc.subjectin-vitroes
dc.subjectneuronses
dc.subjectreceptores
dc.subjectreleasees
dc.titleDepression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPAes
dc.typeinfo:eu-repo/semantics/articlees
dc.rights.holder© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).es
dc.relation.publisherversionhttp://www.sciencedirect.com/science/article/pii/S2211124715007317es
dc.identifier.doi10.1016/j.celrep.2015.07.005
dc.departamentoesFarmacologíaes_ES
dc.departamentoeuFarmakologiaes_ES
dc.subject.categoriaBIOCHEMISTRY AND MOLECULAR BIOLOGY


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