Nebulized and intraperitoneal ketamine have equivalent antidepressant-like effect in the forced swim and tail suspension tests in mice.
Aida A.C. Brandão, D. L. S. Deus, L. A. Duarte-Filho, P. Menezes, Ana Beatriz R. Massaranduba, F. Silva, Luciano A A Ribeiro
Pharmacology, Biochemistry, and Behavior November 8, 2023 DOI: 10.1016/j.pbb.2023.173674 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study Peer reviewed |
|---|---|
| Population | Mice with depression-like behavior induced by corticosterone, dexamethasone, or dexamethasone plus unpredictable chronic mild stress |
| Intervention | Ketamine |
| Dose | 1.3, 2.6, and 5.2 mg/mL nebulized ketamine |
| Measures | forced swimming test (FST), tail suspension test (TST), open field test |
| Topics | Esketamine Ketamine |
| Key points | Nebulized ketamine reduced immobility in the forced swimming and tail suspension tests across three depression-induction models in mice, without changing open field locomotion, and its efficacy matched that of intraperitoneal ketamine. The authors propose nebulization as an inexpensive alternative administration route for behavioral studies in rodents. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 2
- Evaluation of behavioural and neurochemical effects of psilocybin in mice subjected to chronic unpredictable mild stress Translational Psychiatry June 14, 2025
- Shared effects of electroconvulsive shocks and ketamine on neuroplasticity: A systematic review of animal models of depression. Neuroscience & Biobehavioral Reviews September 1, 2024
Cites 12
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