National Institute on Drug Dependence and Beijing Key Laboratory on Drug Dependence Research, Beijing, China.
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.
Biol Psychiatry. 2016 Jun 1;79(11):928-39. doi: 10.1016/j.biopsych.2015.07.007. Epub 2015 Jul 21.
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.
将药物相关刺激物与滥用药物的效果联系起来的药物记忆会导致复发。暴露于与药物相关的环境会导致已巩固的药物记忆处于不稳定状态，在此期间可以进行操作以损害药物记忆。尽管大量证据表明神经元信号在成瘾中起着至关重要的作用，但对于星形胶质细胞-神经元通讯的贡献知之甚少。
在可卡因诱导的条件性位置偏好（CPP）或自我给药后，立即将糖原磷酸化抑制剂 1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇（1,4-dideoxy-1,4-imino-D-arabinitol）微注射到杏仁基底外侧核（BLA）中。在检索后立即通过微透析测量乳酸盐的浓度，并在 24 小时后记录 CPP 评分和鼻触次数。此外，我们在检索后使用反义寡核苷酸破坏 BLA 中星形胶质细胞乳酸盐转运体（单羧酸转运蛋白 1 和 2）的表达，1 天后测试 CPP 的表达，并在检索前 15 分钟将 L-乳酸盐注射到 BLA 中以挽救寡核苷酸的作用。
在检索后立即将 1,4-二脱氧-1,4-亚氨基-D-阿拉伯糖醇注射到 BLA 中可防止随后表达可卡因诱导的 CPP，降低 BLA 中乳酸盐的浓度，并减少可卡因自我给药的鼻触次数。在 BLA 中破坏单羧酸转运蛋白 1 和 2 的表达也会导致可卡因诱导的 CPP 随后表达缺陷，用 L-乳酸盐预处理可挽救该缺陷。
我们的结果表明，BLA 中的星形胶质细胞-神经元乳酸盐转运对于可卡因记忆的再巩固至关重要。
