Related Experiment Video
Updated: Jul 11, 2025
The Forced Swim Test as a Model of Depressive-like Behavior
Published on: March 2, 2015
Nebulized and intraperitoneal ketamine have equivalent antidepressant-like effect in the forced swim and tail
Aida A C Brandão1, Deborah L S Deus2, Luiz A M S Duarte-Filho3
1Curso de mestrado em biociências, Universidade Federal do Vale do São Francisco (UNIVASF), Petrolina, PE 56304-917, Brazil.
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.
Insights
Nebulized ketamine demonstrates antidepressant-like effects in mouse models of depression, offering a rapid and cost-effective alternative for preclinical research. This method shows comparable efficacy to traditional administration routes for studying novel depression treatments.
Area of Science:
- Neuroscience and Pharmacology
- Behavioral Science
- Drug Discovery and Development
Background:
- Major Depressive Disorder (MDD) affects millions globally, with current antidepressants having slow onset, increasing suicide risk.
- Intranasal esketamine shows promise for rapid MDD treatment.
- Preclinical models are crucial for understanding antidepressant mechanisms, but data on alternative administration routes like nebulization is lacking.
Purpose of the Study:
- To investigate the antidepressant-like effects of ketamine administered via nebulization in mouse models.
- To evaluate nebulization as a low-cost, alternative drug administration route for preclinical behavioral studies.
Main Methods:
- Depression-like behavior was induced in mice using corticosterone, dexamethasone, or a combination with unpredictable chronic mild stress (UCMS).
- Mice were treated with varying concentrations of nebulized ketamine.
- Antidepressant effects were assessed using the forced swimming test (FST) and tail suspension test (TST). Locomotor activity was measured via the open field test.
Main Results:
- Nebulized ketamine significantly reduced immobility in FST and TST across different depression models.
- Efficacy of nebulized ketamine was comparable to intraperitoneal administration.
- No significant changes in locomotor activity were observed in the open field test, indicating targeted antidepressant effects.
Conclusions:
- Nebulization is an effective and inexpensive method for administering ketamine in rodent models of depression.
- This approach provides a viable alternative for preclinical research into novel antidepressant therapies.
- Nebulized ketamine offers rapid antidepressant-like effects, supporting its potential in future therapeutic strategies.
