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    Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine

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    Type
    Article
    Authors
    Boury-Jamot, B
    Carrard, A
    Martin, J L
    Halfon, O
    Magistretti, Pierre J. cc
    Boutrel, B
    KAUST Department
    Biological and Environmental Sciences and Engineering (BESE) Division
    Bioscience Program
    Date
    2015-10-27
    Online Publication Date
    2015-10-27
    Print Publication Date
    2016-08
    Permanent link to this record
    http://hdl.handle.net/10754/592604
    
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    Abstract
    A central problem in the treatment of drug addiction is the high risk of relapse often precipitated by drug-associated cues. The transfer of glycogen-derived lactate from astrocytes to neurons is required for long-term memory. Whereas blockade of drug memory reconsolidation represents a potential therapeutic strategy, the role of astrocyte–neuron lactate transport in long-term conditioning has received little attention. By infusing an inhibitor of glycogen phosphorylase into the basolateral amygdala of rats, we report that disruption of astrocyte-derived lactate not only transiently impaired the acquisition of a cocaine-induced conditioned place preference but also persistently disrupted an established conditioning. The drug memory was rescued by L-Lactate co-administration through a mechanism requiring the synaptic plasticity-related transcription factor Zif268 and extracellular signal-regulated kinase (ERK) signalling pathway but not the brain-derived neurotrophic factor (Bdnf). The long-term amnesia induced by glycogenolysis inhibition and the concomitant decreased expression of phospho-ERK were both restored with L-Lactate co-administration. These findings reveal a critical role for astrocyte-derived lactate in positive memory formation and highlight a novel amygdala-dependent reconsolidation process, whose disruption may offer a novel therapeutic target to reduce the long-lasting conditioned responses to cocaine.
    Citation
    Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine 2015 Molecular Psychiatry
    Publisher
    Springer Nature
    Journal
    Molecular Psychiatry
    DOI
    10.1038/mp.2015.157
    Additional Links
    http://www.nature.com/doifinder/10.1038/mp.2015.157
    ae974a485f413a2113503eed53cd6c53
    10.1038/mp.2015.157
    Scopus Count
    Collections
    Articles; Biological and Environmental Science and Engineering (BESE) Division; Bioscience Program

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