• Liang Zhang, Jing Zheng, Shi-Yan Liu, Li-Li Hou, Bo Zhang, and Shao-Wen Tian.
• Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin, Guangxi 541199, China; Department of Anesthesiology, National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China; Department of Anesthesiology, Nanhua Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
• Neuroscience. 2024 Mar 26; 542: 112011-20.

AbstractLactate acts as an important metabolic substrate and signalling molecule modulating neural activities in the brain, and recent preclinical and clinical studies have revealed its antidepressant effect after acute or chronic peripheral administration. However, the neural mechanism underlying the antidepressant effect of lactate, in particular when lactate is acutely administered remains largely unknown. In the current study, we focused on forced swimming test (FST) to elucidate the neural mechanisms through which acute intracerebroventricular (ICV) infusion of lactate exerts antidepressant-like effect. A total of 238 male Sprague Dawley rats were used as experimental subjects. Results showed lactate produced antidepressant-like effect, as indicated by reduced immobility, in a dose- and time-dependent manner. Moreover, the antidepressant-like effect of lactate was dependent of new protein synthesis but not new gene expression, lactate's metabolic effect or hydroxy-carboxylic acid receptor 1 (HCAR1) activation. Furthermore, lactate rapidly promoted dephosphorylation of eukaryotic elongation factor 2 (eEF2) and increased brain-derived neurotrophic factor (BDNF) protein synthesis in the hippocampus in a cyclic adenosine monophosphate (cAMP)-dependent manner. Finally, inhibition of cAMP production blocked the antidepressant-like effect of lactate. These findings suggest that acute administration of lactate exerts antidepressant-like effect through cAMP-dependent protein synthesis.Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.

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