title: Peripheral administration of lactate produces antidepressant-like effects.
abstract: 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.
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: A
authors.initials: A
authors.lastname: Carrard
authors.affiliation: Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Elsayed
authors.affiliation: King Abdullah University of Science and Technology (KAUST), BESE Division, Thuwal, Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Margineanu
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.|Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Boury-Jamot
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: L
authors.initials: L
authors.lastname: Fragnière
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: E M
authors.initials: EM
authors.lastname: Meylan
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.|Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: J-M
authors.initials: JM
authors.lastname: Petit
authors.affiliation: King Abdullah University of Science and Technology (KAUST), BESE Division, Thuwal, Saudi Arabia.
authors.forename: H
authors.initials: H
authors.lastname: Fiumelli
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.|Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.|King Abdullah University of Science and Technology (KAUST), BESE Division, Thuwal, Saudi Arabia.
authors.forename: P J
authors.initials: PJ
authors.lastname: Magistretti
authors.affiliation: Center for Psychiatric Neurosciences, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: J-L
authors.initials: JL
authors.lastname: Martin
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001253:Astrocytes; D003863:Depression / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism; D019344:Lactic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects; D009474:Neurons; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D019344:Lactic Acid