Rats and mice are used most often in tests of behavioral despair, although gerbils and guinea pigs have also been tested. Different procedures are commonly used for rats and mice. It must be emphasized, however, that procedural modifications for particular experimental purposes, e.g., to measure effects following chronic treatment or in genetically modified rodents, are common.
Rats are usually given two trials separated by 24 h. The first trial lasts 15 min and is usually referred to as a pretest. Antidepressant or test drugs are given to rats 2 or 3 times between the trials, as a loading protocol. The second trial lasts only 5 min, because the onset of the immobility is sensitized by the pretest. Antidepressant drug effects are evident in a reduction of duration of immobility during the second test (Porsolt et al. 1977).
Important procedural changes were introduced to the rat forced swimming test because the effects of selective serotonin reuptake inhibitors (► SSRIs) could not be measured using the original testing method (Cryan et al. 2005b; Detke et al. 1995). The modified rat FST measures the frequency of two active behaviors, swimming and climbing, in addition to passive immobility during the second trial. A larger cylinder (at least 20 cm diameter) and higher water level (30 cm depth) was recommended, to keep rodents from positioning themselves to thwart the stressful aspects of the test by using the bottom or sides for support. The new conditions also improved the measurement of swimming behavior produced by the SSRIs. Antidepressant drugs produce different effects on the active behaviors in the modified rat FST. The SSRIs (e.g.,
► fluoxetine, ► paroxetine, ► citalopram) reduce immobility and increase swimming behavior, ► tricyclic anti-depressants and selective ► NARI antidepressants (e.g., desipramine, maprotiline, reboxetine) reduce immobility and increase climbing behavior, and ► SNRI antidepres-sants with effects on both, serotonin and catecholamines or ► monoamine oxidase inhibitors reduce immobility and increase both swimming and climbing behavior (Cryan et al. 2005b; Lucki 1997).
Mice are tested in the forced swimming test or the tail suspension test with just a single trial, lasting usually for 6 min. In the forced swimming test, only the last 4 min may be scored. Cylinders of varying sizes have been used, although larger cylinders (>20 cm) may avoid detecting
► false positives and ► false negatives (SSRIs) in the test. Antidepressant drugs usually have to be given only once to produce a behavioral effect. The total duration of immobility, and the duration until an initial bout of immobility, are usually scored. Some studies have measured immobility, swimming, and climbing behaviors in the mouse FST.
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