Guangxi Key Laboratory of Brain and Cognitive Neuroscience, Faculty of Basic Medical Sciences, Guilin Medical University, Guilin Guangxi, 541199, China; Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang Hunan, 421001, China.
Pharmacy School of Guilin Medical University, Guilin Medical University, Guilin Guangxi, 541199, China.
Physiol Behav. 2021 Dec 1;242:113626. doi: 10.1016/j.physbeh.2021.113626. Epub 2021 Oct 18.
In addition to the antidepressant properties of ketamine at subanesthetic doses, studies have revealed ketamine's influence on memory acquisition, consolidation, and reconsolidation. The effects of acute low-dose ketamine administration on conditioned memory have been investigated extensively in rodents through conditioned fear memory and morphine-induced conditioned place preference. In contrast to conditioned memory, the novel object recognition (NOR) task assesses the natural format of memory by exploiting the rodents' natural preference for novelty. Acute low-dose ketamine administration impairs NOR acquisition and consolidation, but its influence on reconsolidation remains unclear. We investigated the issue as well as the involvement of BDNF/TrkB pathway in this process by administering ketamine (i.p., 10 mg/kg, immediately or 6 h after reactivation, or without reactivation) and ANA-12 (i.p., 0.5 mg/kg, 5 min after ketamine/vehicle administration). ANA-12 is a selective antagonist for the BDNF TrkB receptor. Ketamine administration, immediately after (rather than without) reactivation, significantly increased the NOR preference index, thus suggesting an enhanced memory reconsolidation rather than consolidation. Ketamine exerted no significant effect when administered 6 h after reactivation, thereby suggesting 6 h to be an effective time window. ANA-12 administration significantly reduced the ketamine-induced NOR preference index increase, thus suggesting that the blockage of ketamine improves NOR reconsolidation. However, this blockage had no significant effect on the ketamine-induced hippocampal BDNF level increase. In conclusion, acute low-dose ketamine administration improves NOR memory reconsolidation by increasing hippocampal BDNF levels and subsequent BDNF binding to the TrkB receptor.
除了亚麻醉剂量氯胺酮的抗抑郁特性外，研究还揭示了氯胺酮对记忆获取、巩固和再巩固的影响。通过条件性恐惧记忆和吗啡诱导的条件性位置偏好，在啮齿动物中广泛研究了急性低剂量氯胺酮给药对条件性记忆的影响。与条件性记忆相反，新物体识别（NOR）任务通过利用啮齿动物对新奇事物的自然偏好来评估记忆的自然形式。急性低剂量氯胺酮给药会损害 NOR 的获取和巩固，但对再巩固的影响尚不清楚。我们通过给予氯胺酮（腹腔内，10mg/kg，在重新激活后立即或 6 小时或没有重新激活）和 ANA-12（腹腔内，0.5mg/kg，在氯胺酮/载体给药后 5 分钟）来研究这个问题以及 BDNF/TrkB 通路在此过程中的参与情况。ANA-12 是 BDNF TrkB 受体的选择性拮抗剂。氯胺酮给药，在重新激活后立即（而不是没有），显著增加了 NOR 偏好指数，从而表明再巩固记忆增强，而不是巩固。当在重新激活后 6 小时给予氯胺酮时，氯胺酮没有产生显著影响，从而表明 6 小时是一个有效的时间窗口。ANA-12 给药显著降低了氯胺酮诱导的 NOR 偏好指数增加，从而表明阻断氯胺酮可以改善 NOR 再巩固。然而，这种阻断对氯胺酮诱导的海马 BDNF 水平增加没有显著影响。总之，急性低剂量氯胺酮给药通过增加海马 BDNF 水平和随后 BDNF 与 TrkB 受体结合来改善 NOR 记忆再巩固。
