Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.

重度抑郁症 (MDD) 是一种使人衰弱的疾病，影响着全世界数百万人。目前可用的抗抑郁药物通常需要数周至数月才能充分发挥作用，这导致 MMD 患者自杀行为的风险增加。在鼻内给药方面，艾氯胺酮已成为当前抗抑郁药的替代品，因为它对重度抑郁症患者起效快且效果持久。动物模型对于初步药理学筛选和更好地了解具有抗 MDD 潜力的新药的作用机制很有用。缺乏可用于临床前研究的替代给药途径（口服或注射）的数据。本研究旨在测试使用低成本设备雾化给药时氯胺酮是否对小鼠具有抗抑郁样作用。当皮质酮诱发抑郁样行为的小鼠接受浓度为 1.3、2.6 和 5.2 mg/mL 的雾化氯胺酮治疗时，在强迫游泳试验中，不动性分别减少了 38.6%、62.0% 和 61.1% (FST) 和悬尾测试 (TST) 中分别为 43.6%、42.1% 和 57.9%。当地塞米松诱发抑郁样行为时，氯胺酮雾化使 FST 中的不动性分别降低 79.7%、49.2% 和 44.4%，以及 TST 中的 80.9%、71.4% 和 80.4%。当地塞米松与不可预测的慢性轻度应激 (UCMS) 暴露之间的关联诱发抑郁样行为时，FST 中的不动性分别减少 26.1%、55.3% 和 19.1%。在旷场测试中，接受雾化氯胺酮治疗的小鼠在行走距离或移动时间方面没有表现出显着变化。腹腔注射和雾化氯胺酮的功效相当，这表明雾化可以成为啮齿类动物行为研究的另一种廉价给药途径。