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

Stephanie C Gantz; Erica S Levitt; Nerea Llamosas; Kim A Neve; John T Williams

doi:10.1016/j.celrep.2015.07.005

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

Journal article

Open access

Peer reviewed

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

Stephanie C Gantz, Erica S Levitt, Nerea Llamosas, Kim A Neve and John T Williams

Cell reports (Cambridge), Vol.12(6), pp.944-954

08/11/2015

DOI: 10.1016/j.celrep.2015.07.005

PMCID: PMC4536104

PMID: 26235617

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https://doi.org/10.1016/j.celrep.2015.07.005View

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Abstract

Imbalance 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.

Immunohistochemistry

Levodopa - pharmacology

Animals

Mice, Inbred C57BL

Serotonin - metabolism

Electrophysiology

Female

Male

Synaptic Transmission - drug effects

Mice

Details

Title: Subtitle: Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA
Creators: Stephanie C Gantz - Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
Erica S Levitt - Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA
Nerea Llamosas - Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa 48940, Spain
Kim A Neve - Research Service, VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA
John T Williams - Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: williamj@ohsu.edu
Resource Type: Journal article
Publication Details: Cell reports (Cambridge), Vol.12(6), pp.944-954
Publisher: United States
DOI: 10.1016/j.celrep.2015.07.005
PMID: 26235617
PMCID: PMC4536104
ISSN: 2211-1247
eISSN: 2211-1247
Grant note: DA034388 / NIDA NIH HHS K99 DA038069 / NIDA NIH HHS R01 DA034388 / NIDA NIH HHS DA04523 / NIDA NIH HHS I01 BX000810 / BLRD VA R01 DA004523 / NIDA NIH HHS
Language: English
Date published: 08/11/2015
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute
Record Identifier: 9984065371002771

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