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

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

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

Author(s) -

Stephanie C. Gantz,

Erica S. Levitt,

Nerea Llamosas,

Kim A. Neve,

John T. Williams

Publication year - 2015

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2015.07.005

Subject(s) - dopamine , serotonin , neurotransmission , neuroscience , neurotransmitter , depression (economics) , chemistry , biology , biochemistry , central nervous system , receptor , economics , macroeconomics

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.

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