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

Boury-Jamot, B; Carrard, A; Martin, J L; Halfon, O; Magistretti, Pierre J.; Boutrel, B

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.

Boutrel, B

KAUST Department

Biological and Environmental Sciences and Engineering (BESE) Division
Bioscience Program

Online Publication Date

2015-10-27

Print Publication Date

2016-08

Date

2015-10-27

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