Time to Abolish the Forced Swim Test in Rats for Depression Research (original) (raw)
Related papers
Using the rat forced swim test to assess antidepressant-like activity in rodents
Nature Protocols, 2012
the forced swim test (Fst) is one of the most commonly used animal models for assessing antidepressant-like behavior. this protocol details using the Fst in rats, which takes place over 48 h and is followed by the video analysis of the behavior. the swim test involves the scoring of active (swimming and climbing) or passive (immobility) behavior when rodents are forced to swim in a cylinder from which there is no escape. there are two versions that are used, namely the traditional and modified Fsts, which differ in their experimental setup. For both versions, a pretest of 15 min (although a number of laboratories have used a 10-min pretest with success) is included, as this accentuates the different behaviors in the 5-min swim test following drug treatment. reduction in passive behavior is interpreted as an antidepressant-like effect of the manipulation, provided it does not increase general locomotor activity, which could provide a false positive result in the Fst.
Behavioural Processes, 2020
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Neuroscience & Biobehavioral Reviews, 2018
Systematic reviews can help to evaluate external validity of models We performed a meta-analysis on effects of prototypic antidepressants in the FST As expected, the FST qualitatively detects antidepressant action Results show significant heterogeneity of effect sizes for most drugs We found limited dose-effect size relationship across laboratories laboratories The validity of the test to compare efficacy across conditions is not clear Within experiment D/R curves may help predict hierarchical relationship of interventions
Psychopharmacology, 2002
Abstract Rationale. The forced-swimming test (FST) is utilized to reproduce passive coping responses to stress that may model a relevant aspect of human depression in rodent species. Animals showing high levels of passive responses to the FST are assumed to model pathologically depressed individuals. Objectives. We evaluated sensitivity of FST-induced behavioral responses to the interaction between genetic and environmental influences. Methods. Behavioral responses to FST were evaluated in naive mice of the C57BL/6 and DBA/2 strains, in mice of both strains pre-exposed to FST 14 days before test, and in FST-experienced animals subsequently exposed to 12 days of stress experience (food restriction). Results. C57BL/6 mice are characterized by high propensity to adopt passive coping responses in the FST. Moreover, stress enhances FST-induced immobility in mice of the C57BL/6 strain but reduces this response in DBA/2 mice. Finally, FST-induced immobility in C57BL/6 mice is reduced by chronic treatment with clinically effective antidepressants. Conclusions. These results support the view that behavioral and neural responses to FST exhibited by C57BL/6 mice can be usefully exploited by pre-clinical research on depression.
Forced swimming test in mice: a review of antidepressant activity
Psychopharmacology, 2005
Rationale: Among all animal models, the forced swimming test (FST) remains one of the most used tools for screening antidepressants. Objective: This paper reviews some of the main aspects of the FST in mice. Most of the sensitivity and variability factors that were assessed on the FST are summarized. Mechanisms: We have summarized data found in the literature of antidepressant effects on the FST in mice. From this data set, we have extrapolated information on baseline levels of strain, and sensitivity against antidepressants. Results: We have shown that many parameters have to be considered in this test to gain good reliability. Moreover, there was a fundamental inter-strain difference of response in the FST. Conclusions: The FST is a good screening tool with good reliability and predictive validity. Strain is one of the most important parameters to consider. Swiss and NMRI mice can be used to discriminate the mechanisms of action of drugs. CD-1 seems to be the most useful strain for screening purposes, but this needs to be confirmed with some spontaneous locomotor activity studies.
Effects of Antidepressant Drugs on Rats Bred for Low Activity in the Swim Test
Pharmacology Biochemistry and Behavior, 1998
To determine responsivity to antidepressant medication of Sprague–Dawley rats bred for low activity in the swim test [Swim Low-Active (SwLo) rats], these animals were given different antidepressant drugs via subcutaneously implanted minipumps for 1, 12, or 26 days, and then were tested for activity in the swim test and 2 days later in the open field. Antidepressant drugs given were
Psychopharmacology, 2005
Rationale and objective: This paper describes a new procedure for detecting effective antidepressant treatments. The procedure uses the swim-test susceptible (Susceptible) rat which has been selectively bred to show decreased struggling behavior in a swim test after exposure to a mild stressor. The ability of treatments to block this decrease in swim-test activity was assessed as a method for detecting effective antidepressants. Results: In both male and female Susceptible rats, chronic (14-day) treatment with different antidepressant drugs delivered via osmotic minipump [i.e., three tricyclics (desmethylimipramine, imipramine, amitriptyline), two selective serotonin reuptake inhibitors (fluoxetine and sertraline), a monoamine oxidase inhibitor (phenelzine), and two atypical antidepressants (venlafaxine and bupropion)] all prevented the stress-induced decrease in swim-test struggling normally shown by these rats. Electroconvulsive shock had a similar effect. Unlike antidepressant drugs, 14-day treatment with various nonantidepressant drugs [i.e., a stimulant (amphetamine), an anxiolytic (chlordiazepoxide), an antihistamine (chlorpheniramine), and an anticholinergic (scopolamine)] did not have this effect. Antidepressant drug treatment for 1 day (i.e., acute treatment) was also ineffective in this test. The procedure described above requires use of the Susceptible rat-swim-test resistant rats (i.e., rats selectively bred to be resistant to decreased swim-test activity after exposure to stressful conditions) showed no significant differences in swim-test behavior between stress and nonstress conditions after 14-day drug treatment, and randomly bred Sprague-Dawley rats did not show a decrease in swim-test activity following exposure to the mild stressor that is the basis for the test. Conclusion: These results suggest that the procedure described here, which uses a rat subject that has been bred for vulnerability to stressful conditions, may be a selective screening technique for effective antidepressant treatments.
Neuroscience, 2011
Patients suffering from depression frequently display hyperactivity of the hypothalamic–pituitary–adrenal axis (HPA) resulting in elevated cortisol levels. One main symptom of this condition is anhedonia. There is evidence that exercise training can be used as a rehabilitative intervention in the treatment of depressive disorders. In this scenario, the aim of the present study was to assess the effect of an aerobic exercise training protocol on the depressive-like behavior, anhedonia, induced by repeated dexamethasone administration. The study was carried out on adult male Wistar rats randomly divided into four groups: the “control group” (C), “exercise group” (E), “dexamethasone group” (D) and the “dexamethasone plus exercise group” (DE). The exercise training consisted of swimming (1 h/d, 5 d/wk) for 3 weeks, with an overload of 5% of the rat body weight. Every day rats were injected with either dexamethasone (D/DE) or saline solution (C/E). Proper positive controls, using fluoxetine, were run in parallel. Decreased blood corticosterone levels, reduced adrenal cholesterol synthesis and adrenal weight (HPA disruption), reduced preference for sucrose consumption and increased immobility time (depressive-like behavior), marked hippocampal DNA oxidation, increased IL-10 and total brain-derived neurotrophic factor (BDNF; pro-plus mature-forms) and a severe loss of body mass characterized the dexamethasone-treated animals. Besides increasing testosterone blood concentrations, the swim training protected depressive rats from the anhedonic state, following the same profile as fluoxetine, and also from the dexamethasone-induced impaired neurochemistry. The data indicate that physical exercise could be a useful tool in preventing and treating depressive disorders.▶Exercise training rescue dexamethasone-exposed rats from the anhedonic behavior. ▶The exercise antidepressive effect was found at intensity below the anaerobic threshold. ▶The exercise protected depressive rats also from neurochemical alterations.
Physiology & Behavior, 2009
We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength. Separate groups of rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once per day for 21 consecutive days. Then, half the rats from each group were exposed to the traditional two-day forced swim test and the other half were exposed to our one-day forced swim test. After the forced swim testing, all the rats were tested in an open field and in a wire suspension grip strength test. The CORT injections significantly increased the time spent immobile and decreased the time spent swimming in both versions of the forced swim test. However, they had no significant effect on activity in the open field or grip strength in the wire suspension test. These results show that repeated CORT injections increase depressionlike behavior regardless of the specific parameters of forced swim testing, and that these effects are independent of changes in locomotor activity or muscle strength.