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

Handle URI:
http://hdl.handle.net/10754/592604
Title:
Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine
Authors:
Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, Pierre J. ( 0000-0002-6678-320X ) ; Boutrel, B
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
Disrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine 2015 Molecular Psychiatry
Publisher:
Springer Nature
Journal:
Molecular Psychiatry
Issue Date:
27-Oct-2015
DOI:
10.1038/mp.2015.157
Type:
Article
ISSN:
1359-4184; 1476-5578
Additional Links:
http://www.nature.com/doifinder/10.1038/mp.2015.157
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorBoury-Jamot, Ben
dc.contributor.authorCarrard, Aen
dc.contributor.authorMartin, J Len
dc.contributor.authorHalfon, Oen
dc.contributor.authorMagistretti, Pierre J.en
dc.contributor.authorBoutrel, Ben
dc.date.accessioned2015-12-27T13:25:10Zen
dc.date.available2015-12-27T13:25:10Zen
dc.date.issued2015-10-27en
dc.identifier.citationDisrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaine 2015 Molecular Psychiatryen
dc.identifier.issn1359-4184en
dc.identifier.issn1476-5578en
dc.identifier.doi10.1038/mp.2015.157en
dc.identifier.urihttp://hdl.handle.net/10754/592604en
dc.description.abstractA 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.en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.relation.urlhttp://www.nature.com/doifinder/10.1038/mp.2015.157en
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.en
dc.titleDisrupting astrocyte–neuron lactate transfer persistently reduces conditioned responses to cocaineen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalMolecular Psychiatryen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionCentre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerlanden
dc.contributor.institutionDivision of Child and Adolescent Psychiatry, Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerlanden
dc.contributor.institutionBrain Mind Institute, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerlanden
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorMagistretti, Pierre J.en
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