Zhao Haiting, Li Haoyu, Meng Li, Du Peng, Mo Xin, Gong Mengqi, Chen Jiaxin, Liao Yiwei
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Int J Neuropsychopharmacol. 2024 Dec 28;28(1). doi: 10.1093/ijnp/pyae065.
Understanding drug addiction as a disorder of maladaptive learning, where drug-associated or environmental cues trigger drug cravings and seeking, is crucial for developing effective treatments. Actin polymerization, a biochemical process, plays a crucial role in drug-related memory formation, particularly evident in conditioned place preference paradigms involving drugs like morphine and methamphetamine. However, the role of actin polymerization in the reconsolidation of heroin-associated memories remains understudied.
This study employed a rodent model of self-administered heroin to investigate the involvement of actin polymerization in the reconsolidation of heroin-associated memories. Rats underwent ten days of intravenous heroin self-administration paired with conditioned cues. Subsequently, a 10-day extinction phase aimed to reduce heroin-seeking behaviors. Following this, rats participated in a 15-minute retrieval trial with or without cues. Immediately post-retrieval, rats received bilateral injections of the actin polymerization inhibitor Latrunculin A (Lat A) into the nucleus accumbens core (NACc), a critical brain region for memory reconsolidation.
Immediate administration of Lat A into the NACc post-retrieval significantly reduced cue-induced and heroin-primed reinstatement of heroin-seeking behavior for at least 28 days. However, administering Lat A 6-hour post-retrieval or without a retrieval trial, as well as administering Jasplakionlide prior to memory reactivation did not affect heroin-seeking behaviors.
Inhibiting actin polymerization during the reconsolidation window disrupts heroin-associated memory reconsolidation, leading to decreased heroin-seeking behavior and prevention of relapse. These effects are contingent upon the presence of a retrieval trial and exhibit temporal specificity, shedding light on addiction mechanisms and potential therapeutic interventions.
将药物成瘾理解为一种适应不良学习障碍，其中与药物相关或环境线索会引发药物渴望和寻求行为，这对于开发有效治疗方法至关重要。肌动蛋白聚合作为一种生化过程，在与药物相关的记忆形成中起着关键作用，在涉及吗啡和甲基苯丙胺等药物的条件性位置偏爱范式中尤为明显。然而，肌动蛋白聚合在海洛因相关记忆再巩固中的作用仍未得到充分研究。
本研究采用海洛因自我给药的啮齿动物模型，以研究肌动蛋白聚合在海洛因相关记忆再巩固中的作用。大鼠进行了为期十天的静脉注射海洛因自我给药，并伴有条件线索。随后，进行为期10天的消退期，旨在减少海洛因寻求行为。在此之后，大鼠参与了有或没有线索的15分钟检索试验。检索后立即给大鼠双侧伏隔核核心（NACc）注射肌动蛋白聚合抑制剂Latrunculin A（Lat A），NACc是记忆再巩固的关键脑区。
检索后立即向NACc注射Lat A可显著减少线索诱导和海洛因引发的海洛因寻求行为恢复，至少持续28天。然而，检索后6小时或没有检索试验时注射Lat A，以及在记忆重新激活前注射Jasplakionlide均不影响海洛因寻求行为。
在再巩固窗口期间抑制肌动蛋白聚合会破坏海洛因相关记忆的再巩固，导致海洛因寻求行为减少并预防复发。这些效应取决于检索试验的存在，并表现出时间特异性，为成瘾机制和潜在治疗干预提供了线索。
