Differential behavioral effects of the antidepressants reboxetine, fluoxetine, and moclobemide in a modified forced swim test following chronic treatment
Abstract
Rationale The forced swim test (FST) is the most widely used model for assessing potential antidepressant activity in rodents following acute or short-term treatment. However, few studies have compared the effects of short- and long-term antidepressant treatment on behaviors in the test, despite the need to treat patients chronically to produce clinical effects.Objectives The current studies examined whether antidepressants from different classes produce different behavioral effects following short-term treatment and whether such effects change following administration for a longer duration.Methods The effects of administering short-term (3 days) and long-term (14 days) treatments of antidepressants from three different chemical classes with distinct mechanisms of action via osmotic minipump were examined: the selective norepinephrine reuptake inhibitor reboxetine (10 and 60 mg kg(-1) day(-1)), the selective serotonin reuptake inhibitor fluoxetine (2.5 and 15 mg kg(-1) day(-1)), and the reversible inhibitor of monoamine oxidase moclobemide (2.5 and 15 mg kg(-1) day(-1)). All testing was carried out in a 15-min test with no preswim session in order to negate any confounding aspect of an induction procedure.Results The majority of antidepressant-sensitive behavioral changes were observed in the first 5 min of the test. The low dose of reboxetine failed to alter behavior in the test after 3 days but significantly decreased immobility and increased climbing behavior following administration for 14 days, whereas the high dose of reboxetine was equally effective following 3 and 14 days of treatment. In a similar fashion, the low dose of fluoxetine failed to alter behavior in the test following 3 days, but showed an augmented response on immobility and increased swimming following administration for 14 days. The high dose of fluoxetine was slightly more effective at reducing immobility following administration for 14 days than 3 days. The low dose of moclobemide decreased immobility and increased climbing behavior following treatment for 3 days, but increases in both swimming and climbing behaviors were measured following treatment for 14 days. Treatment with the high dose of moclobemide for 3 days decreased immobility and increased swimming, whereas treatment for 14 days significantly increased both active behaviors (swimming and climbing).Conclusions Antidepressants from three different classes produce different effects on active behaviors in the FST. The effects of antidepressants were augmented following chronic administration for 14 days, especially when given at low doses. This suggests that modifications of the FST can be used to examine the onset of action of antidepressant agents produced by long-term administration.
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The TST assesses changes in escape movements and immobility during an unavoidable stressor.
“Similar to the FST, the TST measures alterations in escape-oriented movements and immobility when placed in an inescapable stressful situation (Cryan et al., 2005).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Cryan et al., 2005
The FST does not reliably reveal SSRI effects.
“One major difference between the FST and the TST is that the FST does not consistently detect SSRI activity (Cryan et al., 2005).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Cryan et al., 2005
In the FST, acute antidepressants, often with home-cage hypolocomotion, increase activity or lower immobility.
“In this test, acute administration of an antidepressant, which is often accompanied by hypolocomotion in the home cage, results in increased activity or reduced immobility in the FST (Cryan et al., 2005).”
From Nicotinic Partial Agonists Varenicline and Sazetidine-A Have Differential Effects on Affective Behavior (2010) · cites this paper as Cryan et al., 2005
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- Authors
- Cryan, J. F., Page, M. E., & Lucki, I.
- Affiliations
- University of Pennsylvania (US)
- Thomas Jefferson University (US)
- Corresponding author
- Lucki, Irwin
- Venue
- Psychopharmacology
- Published
- 2005-07-06
- Volume
- 182
- Issue
- 3
- Pages
- 335-344
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- OpenAlex
- W2028701653
- Cited by
- 321
- References
- 45
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 11 · 2023: 14 · 2022: 25 · 2021: 16 · 2020: 10 · 2019: 16 · 2018: 14 · 2017: 16 · 2016: 20 · 2015: 18 · 2014: 17 · 2013: 14 · 2012: 22
- FWCI
- 7.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Eli Lilly and Company
- U.S. Public Health Service
- National Institute of Mental Health (MH 36262)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- antidepressants, reboxetine, fluoxetine, moclobemide, forced swim test, immobility, climbing behavior, swimming behavior, long-term treatment, short-term treatment, norepinephrine reuptake inhibitors, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, antidepressant mechanism, depression model, osmotic minipump
- MeSH terms
- Reboxetine, Animals, Antidepressive Agents, Behavior, Animal, Fluoxetine, Male, Morpholines, Swimming, Rats, Sprague-Dawley, Moclobemide, Rats
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