Department of Psychology & Neuroscience, University of Guelph, Guelph, Canada.
Department of Neuroscience, Carleton University, Ottawa, Canada.
Addict Biol. 2021 Mar;26(2):e12909. doi: 10.1111/adb.12909. Epub 2020 May 17.
The current study tested the hypothesis that drug withdrawal contributes to the addiction cycle in part because of an action on memory consolidation. Hence, four experiments in male Sprague-Dawley rats compared the effects of precipitated morphine withdrawal and conditioned morphine withdrawal on the consolidation of object memory and on activation of c-Fos in the central nucleus of the amygdala (CeA). It was found that immediate, but not 6 h delayed, post sample administration of 3 mg/kg of naltrexone significantly enhanced object memory in rats maintained, or previously maintained, on 10 mg/kg/day of morphine via osmotic minipumps. To establish whether conditioned withdrawal could also alter object memory, a contextual conditioning procedure was employed whereby morphine-maintained (10 mg/kg/day) animals received naltrexone (3 mg/kg) in a distinctive context (CS+) and vehicle in a separate context (CS-) for 10 days. During conditioning in the CS+, naltrexone suppressed locomotor activity, caused a rapid body weight loss and increased frequency of wet dog shakes. Interestingly, confinement to this CS+ immediately, but not 6 h, after the sample phase, also enhanced object memory. Finally, posttraining naltrexone and exposure to the CS+ both induced significant expression of c-Fos in the CeA. Therefore, this study reports for the first time that both acute precipitated withdrawal and conditioned withdrawal can facilitate memory consolidation, possibly through a common neural pathway that involves the central amygdala.
当前的研究检验了这样一个假设，即药物戒断导致成瘾循环的部分原因是对记忆巩固的作用。因此，在雄性 Sprague-Dawley 大鼠中进行了四项实验，比较了急性吗啡戒断和条件性吗啡戒断对物体记忆巩固和杏仁中央核（CeA）中 c-Fos 激活的影响。结果发现，立即给予而非 6 小时后给予 3mg/kg 的纳曲酮可显著增强通过渗透微型泵维持在 10mg/kg/天吗啡或之前维持在 10mg/kg/天吗啡的大鼠的物体记忆。为了确定条件性戒断是否也能改变物体记忆，采用了情境条件反射程序，即吗啡维持（10mg/kg/天）的动物在 10 天内接受纳曲酮（3mg/kg）在独特的环境（CS+）中和在单独的环境（CS-）中接受载体。在 CS+中进行条件反射时，纳曲酮抑制了运动活动，导致体重迅速下降，并增加了湿狗颤抖的频率。有趣的是，将动物限制在 CS+中，无论是在样本阶段后立即还是 6 小时后，都能增强物体记忆。最后，训练后给予纳曲酮和暴露于 CS+都会导致 CeA 中 c-Fos 的显著表达。因此，本研究首次报道，急性急性戒断和条件性戒断都可以促进记忆巩固，可能通过涉及杏仁中央核的共同神经通路。
