title: Inhibition of Lactate Transport Erases Drug Memory and Prevents Drug Relapse.
abstract: Drug 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.
  
  
  
  Rats 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.
  
  
  
  Injection 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.
  
  
  
  Our results suggest that astrocyte-neuron lactate transport in the BLA is critical for the reconsolidation of cocaine memory.
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Yan
authors: Y
authors: Zhang
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Yanxue
authors: Y
authors: Xue
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Shiqiu
authors: S
authors: Meng
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Yixiao
authors: Y
authors: Luo
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Jie
authors: J
authors: Liang
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Jiali
authors: J
authors: Li
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Sizhi
authors: S
authors: Ai
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Chengyu
authors: C
authors: Sun
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Haowei
authors: H
authors: Shen
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Weili
authors: W
authors: Zhu
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
authors: Ping
authors: P
authors: Wu
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China; Institute of Mental Health/Peking University Sixth Hospital and Key Laboratory of Mental Health, Beijing, China; Peking-Tsinghua Center for Life Sciences and Peking University-International Data Group/McGovern Institute for Brain Research, Peking University, Beijing, China.
authors: Lin
authors: L
authors: Lu
authors: National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China. Electronic address: shijie@bjmu.edu.cn.
authors: Jie
authors: J
authors: Shi
mesh_terms: D000818:Animals; D001089:Arabinose / Q000494:pharmacology*; D066272:Basolateral Nuclear Complex / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000187:drug effects / Q000502:physiology; D050113:Imino Furanoses / Q000494:pharmacology*; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects* / Q000502:physiology; D027501:Monocarboxylic Acid Transporters / Q000037:antagonists & inhibitors / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D055502:Secondary Prevention; D012646:Self Administration; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D013402:Sugar Alcohols / Q000494:pharmacology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D050113:Imino Furanoses; D027501:Monocarboxylic Acid Transporters; D011619:Psychotropic Drugs; D013402:Sugar Alcohols; C058137:1,4-dideoxy-1,4-iminoarabinitol; D019344:Lactic Acid; D001089:Arabinose; D003042:Cocaine
keywords: Basolateral amygdale; Cocaine; Lactate transport; Reconsolidation; Relapse; Retrieval