title: Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA.
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.
authors.affiliation: Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Gantz
authors.affiliation: Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Levitt
authors.affiliation: Department of Pharmacology, Faculty of Medicine and Dentistry, University of the Basque Country UPV/EHU, Leioa 48940, Spain.
authors.forename: Nerea
authors.initials: N
authors.lastname: Llamosas
authors.affiliation: Research Service, VA Portland Health Care System and Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Neve
authors.affiliation: Vollum Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: williamj@ohsu.edu.
authors.forename: John T
authors.initials: JT
authors.lastname: Williams
mesh_terms: D000818:Animals; D004594:Electrophysiology; D005260:Female; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D012701:Serotonin; D007980:Levodopa