Chen Ya-Yun, Zhang Li-Bo, Li Yue, Meng Shi-Qiu, Gong Yi-Miao, Lu Lin, Xue Yan-Xue, Shi Jie
Department of Pharmacology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Beijing Key Laboratory of Drug Dependence, National Institute on Drug Dependence, Peking University, Beijing, China.
Front Mol Neurosci. 2019 Jul 2;12:157. doi: 10.3389/fnmol.2019.00157. eCollection 2019.
Methamphetamine abuse has become a serious public health problem. However, effective treatment for methamphetamine addiction remains elusive, especially considering its high rate of relapse after treatment. A conditioned stimulus (CS) memory retrieval-extinction procedure has been demonstrated to decrease reinstatement of cocaine, heroin, and alcohol seeking in rats, and to reduce cue-induced cravings in heroin and nicotine addicts. The goal of the present study is to explore the effect of the CS memory retrieval-extinction procedure on methamphetamine seeking in rats and the underlying mechanisms. We found that daily retrieval of methamphetamine-associated memories 1 h before extinction sessions decreased subsequent drug priming-induced reinstatement, spontaneous recovery, and renewal of methamphetamine seeking. We also found that retrieval of methamphetamine-associated memories induced neuronal activation in the basolateral amygdala (BLA), while presenting extinction within the time window of reconsolidation abolished the neuronal activation in BLA. These results indicate that the CS memory retrieval-extinction procedure could prevent reconsolidation of methamphetamine memory traces in BLA and subsequent methamphetamine craving and relapse.
甲基苯丙胺滥用已成为一个严重的公共卫生问题。然而,针对甲基苯丙胺成瘾的有效治疗方法仍然难以捉摸,尤其是考虑到其治疗后高复发率。一种条件刺激(CS)记忆提取-消退程序已被证明可减少大鼠对可卡因、海洛因和酒精的觅求复燃,并减少海洛因和尼古丁成瘾者的线索诱导渴望。本研究的目的是探讨CS记忆提取-消退程序对大鼠甲基苯丙胺觅求的影响及其潜在机制。我们发现,在消退训练前1小时每天提取与甲基苯丙胺相关的记忆可减少随后药物激发诱导的复燃、自发恢复以及甲基苯丙胺觅求的恢复。我们还发现,提取与甲基苯丙胺相关的记忆会诱导基底外侧杏仁核(BLA)中的神经元激活,而在重新巩固的时间窗口内进行消退则消除了BLA中的神经元激活。这些结果表明,CS记忆提取-消退程序可以防止BLA中甲基苯丙胺记忆痕迹的重新巩固以及随后的甲基苯丙胺渴望和复发。