Ketamine is a dissociative anesthetic that has been shown to have antidepressant effects in humans and has been proposed as a potential treatment for mood disorders such as posttraumatic stress disorder and aggression. However, previous studies from our lab and others have demonstrated that ketamine's effects are highly context- and dose-dependent. In a recent study, we found that 10 mg/kg ketamine could exacerbate the effects of early life stress on excessive aggression in mice. To further investigate, the effect of ketamine on moods, such as fear, anxiety, depression, and aggression, we used a mouse model of early life stress, involving chronic social isolation followed by acute traumatic stress in the form of noncontingent, unpredictable foot shock during adolescence. We find this is necessary to induce long-lasting excessive aggression in a novel environment. Seven- to eight-week-old socially isolated mice were given IP injections of 10 mg/kg ketamine 30 min before being subjected to foot shock and then assessed 7 days later for changes in sociability, aggression, mobility, anxiety-like behavior, and depression-like behavior. The results show that ketamine selectively increases long-lasting aggression in mice exposed to foot shock, but does not affect mood-related behaviors or locomotion. These findings suggest that during early life stress, ketamine may exert its effects by specifically targeting aggression brain circuitry that is distinct from brain circuits responsible for nonaggressive social or emotional behaviors. Therefore, while ketamine may be a promising treatment for various mood disorders, caution should be exercised when using ketamine to treat disorders associated with early life stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

中文翻译：

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单剂量的氯胺酮可增强小鼠早期生活压力引起的攻击性，但对恐惧记忆、焦虑样行为或抑郁样行为没有影响。

氯胺酮是一种解离麻醉剂，已被证明对人类具有抗抑郁作用，并被提议作为治疗创伤后应激障碍和攻击性等情绪障碍的潜在方法。然而，我们实验室和其他实验室之前的研究表明，氯胺酮的作用高度依赖于环境和剂量。在最近的一项研究中，我们发现 10 毫克/千克氯胺酮可能会加剧早期生活压力对小鼠过度攻击性的影响。为了进一步研究氯胺酮对恐惧、焦虑、抑郁和攻击性等情绪的影响，我们使用了早期生活压力的小鼠模型，包括长期的社会隔离，以及随后以非偶然、不可预测的足部电击形式出现的急性创伤性压力青春期期间。我们发现这对于在新环境中引发持久的过度攻击性是必要的。7 至 8 周大的社会隔离小鼠在受到足部电击前 30 分钟腹腔注射 10 毫克/千克氯胺酮，然后在 7 天后评估其社交能力、攻击性、活动能力、焦虑样行为和行为的变化。类似抑郁症的行为。结果表明，氯胺酮选择性地增加足部电击小鼠的长期攻击性，但不影响与情绪相关的行为或运动。这些发现表明，在早期生活压力期间，氯胺酮可能通过专门针对攻击性脑回路发挥其作用，该脑回路与负责非攻击性社交或情绪行为的脑回路不同。因此，虽然氯胺酮可能是治疗各种情绪障碍的一种有前途的治疗方法，但在使用氯胺酮治疗与早期生活压力相关的疾病时应谨慎行事。（PsycInfo 数据库记录 (c) 2023 APA，保留所有权利）。