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

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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-DOPAaugmented 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-HT1Areceptor- 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.

Original languageEnglish (US)
Pages (from-to)944-954
Number of pages11
JournalCell Reports
Issue number6
StatePublished - 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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