Peripheral administration of lactate produces antidepressant-like effects

A Carrard, M Elsayed, Michael B. Margineanu, B Boury-Jamot, L Fragnière, E M Meylan, J-M Petit, Hubert Fiumelli, Pierre J. Magistretti, J-L Martin

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


In addition to its role as metabolic substrate that can sustain neuronal function and viability, emerging evidence supports a role for l-lactate as an intercellular signaling molecule involved in synaptic plasticity. Clinical and basic research studies have shown that major depression and chronic stress are associated with alterations in structural and functional plasticity. These findings led us to investigate the role of l-lactate as a potential novel antidepressant. Here we show that peripheral administration of l-lactate produces antidepressant-like effects in different animal models of depression that respond to acute and chronic antidepressant treatment. The antidepressant-like effects of l-lactate are associated with increases in hippocampal lactate levels and with changes in the expression of target genes involved in serotonin receptor trafficking, astrocyte functions, neurogenesis, nitric oxide synthesis and cAMP signaling. Further elucidation of the mechanisms underlying the antidepressant effects of l-lactate may help to identify novel therapeutic targets for the treatment of depression.
Original languageEnglish (US)
Pages (from-to)392-399
Number of pages8
JournalMolecular Psychiatry
Issue number2
StatePublished - Oct 18 2016

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank Dr I Allaman for critical reading of the manuscript and C Martin for assistance with preliminary experiments. This work was supported by the National Center of Competence in Research (NCCR) Synapsy, the Préfargier Foundation and by funding from King Abdullah University of Science and Technology (KAUST).


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