Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.

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Version: Final published version
Serval ID
serval:BIB_EF352DE3FE94
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Disrupting astrocyte-neuron lactate transfer persistently reduces conditioned responses to cocaine.
Journal
Molecular Psychiatry
Author(s)
Boury-Jamot B., Carrard A., Martin J.L., Halfon O., Magistretti P.J., Boutrel B.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
21
Number
8
Pages
1070-1076
Language
english
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.
Pubmed
Web of science
Open Access
Yes
Create date
02/11/2015 14:48
Last modification date
20/08/2019 16:16
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