Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse

Abstract

BackgroundDrug memories that associate drug-paired stimuli with the effects of abused drugs contribute to relapse. Exposure to drug-associated contexts causes consolidated drug memories to be in a labile state, during which manipulations can be given to impair drug memories. Although substantial evidence demonstrates the crucial role of neuronal signaling in addiction, little is known about the contribution of astrocyte-neuron communication. MethodsRats were trained for cocaine-induced conditioned place preference (CPP) or self-administration and microinjected with the glycogen phosphorylation inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol into the basolateral amygdala (BLA) immediately after retrieval. The concentration of lactate was measured immediately after retrieval via microdialysis, and the CPP score and number of nosepokes were recorded 24 hours later. Furthermore, we used antisense oligodeoxynucleotides to disrupt the expression of astrocytic lactate transporters (monocarboxylate transporters 1 and 2) in the BLA after retrieval, tested the expression of CPP 1 day later, and injected L-lactate into the BLA 15 minutes before retrieval to rescue the effects of the oligodeoxynucleotides. ResultsInjection of 1,4-dideoxy-1,4-imino-D-arabinitol into the BLA immediately after retrieval prevented the subsequent expression of cocaine-induced CPP, decreased the concentration of lactate in the BLA, and reduced the number of nosepokes for cocaine self-administration. Disrupting the expression of monocarboxylate transporters 1 and 2 in the BLA also caused subsequent deficits in the expression of cocaine-induced CPP, which was rescued by pretreatment with L-lactate. ConclusionsOur results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory.