PDF(Pubmed)
Abstract：
Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine\'s antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes. Furthermore, the assessment of trait negative emotionality holds promise to link findings in healthy participants to potential AD mechanisms of ketamine. In this double-blind, placebo-controlled, randomized, single dose, parallel-group study, we collected resting-state fMRI data before, during, and 24 h after ketamine administration in a sample of 75 healthy male and female participants who were randomly allocated to one of three treatment conditions (ketamine, ketamine with lamotrigine pre- treatment, placebo). Spontaneous brain activity was extracted from two ventral and one dorsal subregions of the ACC. Our results showed activity decreases during the administration of ketamine in all three ACC subregions. However, only in the ventral subregions of the ACC this effect was attenuated by lamotrigine. 24 h after administration, ACC activity returned to baseline levels, but group differences were observed between the lamotrigine and the ketamine group. Trait negative emotionality was closely linked to activity changes in the subgenual ACC after ketamine administration. These results contribute to an understanding of the functional significance of ketamine effects in different subregions of the ACC by combining an approach to modulate glutamate release with the assessment of multiple timepoints and associations with trait negative emotionality in healthy participants.
摘要：
神经影像学研究已经确定前扣带皮质（ACC）是人类大脑中氯胺酮的主要目标之一，这可能与氯胺酮的抗抑郁（AD）作用机制有关。然而,由于方法论的不同，不同的调查人群，和不同的测量时间点，结果不一致，观察到的大脑变化的功能意义仍然是一个公开辩论的问题。拉莫三嗪在急性氯胺酮给药过程中抑制谷氨酸释放提供了机会，可以进一步了解氯胺酮诱导的大脑变化的功能意义。此外，特质负性情绪的评估有望将健康参与者的发现与氯胺酮的潜在AD机制联系起来.在这个双盲中，安慰剂对照,随机化，单剂量,平行组研究,我们之前收集了静息状态的功能磁共振成像数据，during,和24小时后氯胺酮在75名健康男性和女性参与者的样本中被随机分配到三种治疗条件之一（氯胺酮，氯胺酮与拉莫三嗪预处理，安慰剂)。从ACC的两个腹侧和一个背侧亚区域提取自发性脑活动。我们的结果表明，在所有三个ACC亚区中氯胺酮给药期间，活性均降低。然而,拉莫三嗪仅在ACC的腹侧亚区减弱了这种作用.给药后24小时，ACC活动恢复到基线水平，但在拉莫三嗪和氯胺酮组之间观察到组间差异。给予氯胺酮后，特质负性情绪与亚基因ACC的活性变化密切相关。通过将调节谷氨酸释放的方法与对多个时间点的评估以及与健康参与者的特质负性情绪的关联相结合，这些结果有助于理解氯胺酮在ACC不同亚区中的作用的功能意义。
