Citalopram counteracts depressive-like symptoms evoked by chronic social stress in rats

Abstract

Recently, we have described a new model of chronic social stress in rats, based on the resident-intruder paradigm. In this model, rats show behavioural changes that may be considered correlates of depressive symptoms, such as anhedonia and motivational deficits. The present study was designed for pharmacological validation of this model. Animals were socially stressed for 5 weeks and, in parallel, after the first week of stress, they were subjected to chronic (4 weeks) treatment with the antidepressant drug citalopram. The drug was administered via drinking water (30 mg/kg). The optimal dose of citalopram was determined in a pilot study. After 4 weeks of treatment, plasma levels of citalopram and its metabolite were found to be within the human therapeutic range. The effects of social stress and citalopram treatment were assessed by behavioural tests. Chronically stressed rats showed reduced locomotor and exploratory activity, reduced sucrose preference and increased immobility time in the forced swimming test. Chronic oral administration of citalopram abolished those effects and normalized behaviours related to motivation and reward sensitivity. These observations provide evidence for the predictive validity of the chronic social stress paradigm as a model of depressive symptoms in rats.

Depression-related anhedonic behaviors caused by immobilization stress: a comparison with nicotine-induced depression-like behavioral alterations and effects of nicotine and/or "antidepressant" drugs

“…Although the contributions of more than a single monoamine-related mechanisms, including dopamine-related mechanisms, were suggested by previous studies (Miller et al, 1996;Perona et al, 2008), the selective serotonin reuptake inhibitor FL, as well as AT and CL, the drugs which inhibit the reuptake of serotonin and norepinephrine, caused -mental model, which is consistent with previous studies (Rygula et al, 2006;Strekalova et al, 2006). On the other hand, in the IM-NC group of mice co-treated with AT, -erence index were not caused by NC, which antagonized the IM-induced attenuated preference for sucrose in the IM-NC group without the co-treatment (Figs.…”

Rapid Antidepressant Action and Restoration of Excitatory Synaptic Strength After Chronic Stress by Negative Modulators of Alpha5-Containing GABAA Receptors

“…The loss of the rewarding properties of these stimuli is considered to be analogous to anhedonia, or the inability to experience reward, a core symptom of human depression. Importantly, normal behavior in both the sucrose preference test (Rygula et al, 2006) and social interaction test (Berton et al, 2006) is restored with chronic, but not acute, administration of SSRIs, thus providing a strong predictive indication of the potential human antidepressant efficacy of α5-selective negative allosteric modulators.…”

“…Rats were given a choice between two bottles containing tap water or 1% sucrose solution (Rygula et al, 2006). Testing was conducted overnight (16 h), including the full duration of their dark phase.…”

Chronic Social Stress Inhibits Cell Proliferation in the Adult Medial Prefrontal Cortex: Hemispheric Asymmetry and Reversal by Fluoxetine Treatment

“…This approach is in contrast to clinical practice in which treatment is restricted to sufferers of affective disorders, and antidepressant medication or electroconvulsive stimulation in nondepressed individuals almost certainly does not produce the same neural changes as when these treatments are applied to depressed patients. In the present study, we applied the chronic social defeat paradigm in rats, which is regarded as an animal model of depression (Rygula et al, 2005(Rygula et al, , 2006a, to investigate the effect of chronic stress exposure and concomitant fluoxetine treatment on cell proliferation and neurogenesis in limbic structures, such as the hippocampal formation and PFC. To determine whether these interventions have a region-specific effect, we also analyzed other, nonlimbic brain areas such as the primary motor cortex and subventricular zone.…”