Anhedonia and motivational deficits in rats: Impact of chronic social stress

Ryguła, Rafał; Abumaria, Nashat; Flügge, Gabriele; Fuchs, Eberhard; Rüther, Eckart; Havemann-Reinecke, Ursula

doi:10.1016/j.bbr.2005.03.009

Cited by 488 publications

(370 citation statements)

References 48 publications

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“…The chronic social stress in these rats is based on the resident-intruder paradigm originally described by Miczek (1991) and Koolhaas et al (1997). Social defeat was induced as reported in Rygula et al (2005). The female resident rats were removed from the residents' cages before the social defeat procedure.…”

Section: Animals Experimental Procedures and Fluoxetine Treatmentmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

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317

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Profound neuroplastic changes have been demonstrated in various limbic structures after chronic stress exposure and antidepressant treatment in animal models of mood disorders. Here, we examined in rats the effect of chronic social stress and concomitant antidepressant treatment on cell proliferation in the medial prefrontal cortex (mPFC). We also examined possible hemispheric differences. Animals were subjected to 5 weeks of daily social defeat by an aggressive conspecific and received concomitant, daily, oral fluoxetine (10 mg/kg) during the last 4 weeks. Bromodeoxyuridine (BrdU) labeling and quantitative stereological techniques were used to evaluate the treatment effects on proliferation and survival of newborn cells in limbic structures such as the mPFC and the hippocampal dentate gyrus, in comparison with nonlimbic structures such as the primary motor cortex and the subventricular zone. Phenotypic analysis showed that neurogenesis dominated the dentate gyrus, whereas in the mPFC most newborn cells were glia, with smaller numbers of endothelial cells. Chronic stress significantly suppressed cytogenesis in the mPFC and neurogenesis in the dentate gyrus, but had minor effect in nonlimbic structures. Fluoxetine treatment counteracted the inhibitory effect of stress. Hemispheric comparison revealed that the rate of cytogenesis was significantly higher in the left mPFC of control animals, whereas stress inverted this asymmetry, yielding a significantly higher incidence of newborn cells in the right mPFC. Fluoxetine treatment abolished hemispheric asymmetry in both control and stressed animals. These pronounced changes in gliogenesis after chronic stress exposure may relate to the abnormalities of glial cell numbers reported in the frontolimbic areas of depressed patients.

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Section: Animals Experimental Procedures and Fluoxetine Treatmentmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Czéh

Müller-Keuker

Ryguła

et al. 2006

Neuropsychopharmacol

Self Cite

317

221

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“…Thus, for the functional validation of some transcripts identified as possible drug targets, further studies will be necessary to assess the effect of transcriptional regulation in one or more rodent models of depression. [38][39][40][41][42][43] Another apparent limitation is that transcriptional profiles for the different treatments were compared only at the time points corresponding to clinical efficacy, which differed for each treatment being 2 days for ECT, 1 day for SD and 14 days for FLX. Thus, a comparative analysis of transcriptional changes induced at the same time points for all treatments is missing.…”

Section: Number Of Transcripts Affected By Single and Multiple Treatmmentioning

confidence: 99%

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

et al. 2006

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The significant proportion of depressed patients that are resistant to monoaminergic drug therapy and the slow onset of therapeutic effects of the selective serotonin reuptake inhibitors (SSRIs)/serotonin/noradrenaline reuptake inhibitors (SNRIs) are two major reasons for the sustained search for new antidepressants. In an attempt to identify common underlying mechanisms for fast-and slow-acting antidepressant modalities, we have examined the transcriptional changes in seven different brain regions of the rat brain induced by three clinically effective antidepressant treatments: electro convulsive therapy (ECT), sleep deprivation (SD), and fluoxetine (FLX), the most commonly used slow-onset antidepressant. Each of these antidepressant treatments was applied with the same regimen known to have clinical efficacy: 2 days of ECT (four sessions per day), 24 h of SD, and 14 days of daily treatment of FLX, respectively. Transcriptional changes were evaluated on RNA extracted from seven different brain regions using the Affymetrix rat genome microarray 230 2.0. The gene chip data were validated using in situ hybridization or autoradiography for selected genes. The major findings of the study are:1. The transcriptional changes induced by SD, ECT and SSRI display a regionally specific distribution distinct to each treatment. 2. The fast-onset, short-lived antidepressant treatments ECT and SD evoked transcriptional changes primarily in the catecholaminergic system, whereas the slow-onset antidepressant FLX treatment evoked transcriptional changes in the serotonergic system. 3. ECT and SD affect in a similar manner the same brain regions, primarily the locus coeruleus, whereas the effects of FLX were primarily in the dorsal raphe and hypothalamus, suggesting that both different regions and pathways account for fast onset but short lasting effects as compared to slow-onset but long-lasting effects. However, the similarity between effects of ECT and SD is somewhat confounded by the fact that the two treatments appear to regulate a number of transcripts in an opposite manner. 4. Multiple transcripts (e.g. brain-derived neurotrophic factor (BDNF), serum/glucocorticoidregulated kinase (Sgk1)), whose level was reported to be affected by antidepressants or behavioral manipulations, were also found to be regulated by the treatments used in the present study. Several novel findings of transcriptional regulation upon one, two or all three treatments were made, for the latter we highlight homer, erg2, HSP27, the proto oncogene ret, sulfotransferase family 1A (Sult1a1), glycerol 3-phosphate dehydrogenase (GPD3), the orphan receptor G protein-coupled receptor 88 (GPR88) and a large number of expressed sequence tags (ESTs). 5. Transcripts encoding proteins involved in synaptic plasticity in the hippocampus were strongly affected by ECT and SD, but not by FLX.The novel transcripts, concomitantly regulated by several antidepressant treatments, may represent novel targets for fast onset, long-duration antidepressants.

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“…However, although many pre-clinical studies attempting to model aspects of depression have focused on behaviors thought to represent anhedonia, reduced locomotor activity or behavioral despair (eg, Lu et al, 2006;Rygula et al, 2005;Willner, 1997;Willner and Mitchell, 2002), relatively few have attempted to model cognitive impairments or state anxiety associated with depression.…”

Section: Introductionmentioning

confidence: 99%

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

Bondi

Rodríguez

Gould

et al. 2007

Neuropsychopharmacol

353

263

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Chronic stress is a risk factor for the development of many psychopathological conditions in humans, including major depression and anxiety disorders. There is a high degree of comorbidity of depression and anxiety. Moreover, cognitive impairments associated with frontal lobe dysfunction, including deficits in cognitive set-shifting and behavioral flexibility, are increasingly recognized as major components of depression, anxiety disorders, and other stress-related psychiatric illnesses. To begin to understand the neurobiological mechanisms underlying the cognitive and emotional consequences of chronic stress, it is necessary to employ an animal model that exhibits similar effects. In the present study, a rat model of chronic unpredictable stress (CUS) consistently induced a cognitive impairment in extradimensional set shifting capability in an attentional set shifting test, suggesting an alteration in function of the medial prefrontal cortex. CUS also increased anxiety-like behavior on the elevated plus-maze. Further, chronic treatment both with the selective norepinephrine reuptake blocker, desipramine (7.5 mg/kg/day), and the selective serotonin reuptake blocker, escitalopram (10 mg/kg/ day), beginning 1 week before CUS treatment and continuing through the behavioral testing period, prevented the CUS-induced deficit in extradimensional set-shifting. Chronic desipramine treatment also prevented the CUS-induced increase in anxiety-like behavioral reactivity on the plus-maze, but escitalopram was less effective on this measure. Thus, CUS induced both cognitive and emotional disturbances that are similar to components of major depression and anxiety disorders. These effects were prevented by chronic treatment with antidepressant drugs, consistent also with clinical evidence that relapse of depressive episodes can be prevented by antidepressant drug treatment.

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Anhedonia and motivational deficits in rats: Impact of chronic social stress

Cited by 488 publications

References 48 publications

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

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

Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine

Chronic Unpredictable Stress Induces a Cognitive Deficit and Anxiety-Like Behavior in Rats that is Prevented by Chronic Antidepressant Drug Treatment

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