DataSheet_1_Liposome-Encapsulated Morphine Affords a Prolonged Analgesia While Facilitating Extinction of Reward and Aversive Memories.pdf

Morphine is thoroughly used for pain control; however, it has a high addictive potential. Opioid liposome formulations produce controlled drug release and have been thoroughly tested for pain treatment although their role in addiction is still unknown. This study investigated the effects of free morphine and morphine encapsulated in unilamellar and multilamellar liposomes on antinociception and on the expression and extinction of the positive and negative memories associated with environmental cues. The hot plate test was used to measure central pain. The rewarding effects of morphine were analyzed by the conditioned-place preference (CPP) test, and the aversive aspects of naloxone-precipitated morphine withdrawal were evaluated by the conditioned-place aversion (CPA) paradigm. Our results show that encapsulated morphine yields prolonged antinociceptive effects compared with the free form, and that CPP and CPA expression were similar in the free- or encapsulated-morphine groups. However, we demonstrate, for the first time, that morphine encapsulation reduces the duration of reward and aversive memories, suggesting that this technological process could transform morphine into a potentially less addictive drug. Morphine encapsulation in liposomes could represent a pharmacological approach for enhancing extinction, which might lead to effective clinical treatments in drug addiction with fewer side effects.

吗啡（Morphine）广泛用于疼痛控制，但其成瘾潜力极高。阿片类脂质体制剂可实现药物控释，且已在疼痛治疗领域完成充分测试，但其在成瘾过程中的作用仍不明晰。本研究探究了游离吗啡，以及包封于单室脂质体（unilamellar liposomes）、多室脂质体（multilamellar liposomes）中的吗啡，对镇痛作用（antinociception），以及与环境线索相关的正负性记忆的表达与消退的影响。本研究采用热板试验（hot plate test）测定中枢性疼痛；通过条件性位置偏爱（conditioned-place preference, CPP）实验分析吗啡的奖赏效应；并采用条件性位置厌恶（conditioned-place aversion, CPA）范式评估纳洛酮催促的吗啡戒断反应的厌恶特征。研究结果显示，相较于游离态吗啡，包封型吗啡的镇痛作用持续时间更长；且游离吗啡组与包封吗啡组的CPP、CPA表达水平无显著差异。但本研究首次证实，脂质体包封吗啡可缩短奖赏与厌恶记忆的持续时长，提示该技术可将吗啡改造为成瘾潜力更低的潜在药物。脂质体包封吗啡有望成为一种增强记忆消退的药理学手段，或可开发出副作用更少、疗效更优的药物成瘾临床治疗方案。