The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum

Brenes, Juan C.; Fornaguera, Jaime

doi:10.1016/j.bbr.2008.10.036

Cited by 108 publications

(57 citation statements)

References 40 publications

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“…The results presented in figure 2 show a significant decrease in swimming, followed by an increase in immobility time in stressed animals (p < 0.05), while climbing remained unaffected. This result is in accordance with data obtained from other laboratories where a statistically significant increase of immobility time in stressed animals was also detected [25,26]. …”

Section: Resultssupporting

confidence: 83%

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Djordjević¹,

Djordjević²,

Adžić³

et al. 2012

Neuropsychobiology

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Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology.

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Section: Resultssupporting

confidence: 83%

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Djordjević¹,

Djordjević²,

Adžić³

et al. 2012

Neuropsychobiology

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“…The antidepressant efficacy of MAP4343 was investigated in the isolation-rearing model that has been shown to induce "depressive-like" behaviors including recognition memory deficits (5), increased anxiety (16), and increased passive coping behavior (17). In the isolation-rearing model of depression, MAP4343 demonstrated clear antidepressant activity and important advantages compared with FLX.…”

Section: Discussionmentioning

confidence: 99%

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Bianchi¹,

Baulieu²

2012

Proc. Natl. Acad. Sci. U.S.A.

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Emerging evidence suggests that the pathogenesis of depressive disorders (DDs) is associated with neuronal abnormalities in brain microtubule function, including changes in α-tubulin isoforms. Currently available antidepressant drugs may act by rescuing these alterations, but only after long-term treatment explaining their delayed therapeutic efficacy. The microtubule associated protein type-2 (MAP-2) modulates neuronal microtubule dynamics. Our hypothesis is that MAP-2 represents an innovative target for the treatment of DDs. The synthetic pregnenolone-derivative MAP4343 (3β-methoxy-pregnenolone) binds MAP-2 in vitro and increases its ability to stimulate tubulin assembly. Here, we show that MAP4343 has antidepressant efficacy in rats and advantages compared with the selective serotonin reuptake inhibitor (SSRI) fluoxetine. A single injection of MAP4343 changes the expression of α-tubulin isoforms indicative of increased microtubule dynamics in the hippocampus of naïve Sprague–Dawley rats, whereas fluoxetine had no effects. MAP4343 has positive efficacy in the rat forced swimming test (FST), the most used assay to screen potential antidepressant drugs by decreasing immobility behavior. In the rat isolation-rearing model of depression, administration of MAP4343 showed more rapid and more persistent efficacy compared with fluoxetine in recovering “depressive-like” behaviors. These effects were accompanied by modifications of α-tubulin isoforms in the hippocampus, amygdala, and prefrontal cortex. Our findings suggest the potential therapeutic use of MAP4343 for the treatment of DDs, based on a unique mechanism of action.

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“…Despite the fact that rodent models are developed for homogeneity across subjects reducing confounding variables, such as genetic modifications and experiential factors (injury variables, individual epigenetic variability, and social housing conditions), that are known to affect depression-like behavior in rodents, there are clear differences in the expression of depression-like behaviors. [78][79][80] The evidence of depression in some subjects, but not others, is intriguing, but is commensurate with the human clinical condition. Indeed, in both human and animal populations, it is clear that not all individuals display all of the symptoms, or even the same constellation of symptoms, of depression.…”

mentioning

confidence: 98%

Assessment of Depression in a Rodent Model of Spinal Cord Injury

Luedtke

Bouchard

Woller

et al. 2014

Journal of Neurotrauma

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Despite an increased incidence of depression in patients after spinal cord injury (SCI), there is no animal model of depression after SCI. To address this, we used a battery of established tests to assess depression after a rodent contusion injury. Subjects were acclimated to the tasks, and baseline scores were collected before SCI. Testing was conducted on days 9-10 (acute) and 19-20 (chronic) postinjury. To categorize depression, subjects' scores on each behavioral measure were averaged across the acute and chronic stages of injury and subjected to a principal component analysis. This analysis revealed a two-component structure, which explained 72.2% of between-subjects variance. The data were then analyzed with a hierarchical cluster analysis, identifying two clusters that differed significantly on the sucrose preference, open field, social exploration, and burrowing tasks. One cluster (9 of 26 subjects) displayed characteristics of depression. Using these data, a discriminant function analysis was conducted to derive an equation that could classify subjects as ''depressed'' on days 9-10. The discriminant function was used in a second experiment examining whether the depression-like symptoms could be reversed with the antidepressant, fluoxetine. Fluoxetine significantly decreased immobility in the forced swim test (FST) in depressed subjects identified with the equation. Subjects that were depressed and treated with saline displayed significantly increased immobility on the FST, relative to not depressed, saline-treated controls. These initial experiments validate our tests of depression, generating a powerful model system for further understanding the relationships between molecular changes induced by SCI and the development of depression.

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The effect of chronic fluoxetine on social isolation-induced changes on sucrose consumption, immobility behavior, and on serotonin and dopamine function in hippocampus and ventral striatum

Cited by 108 publications

References 40 publications

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

Effects of Chronic Social Isolation on Wistar Rat Behavior and Brain Plasticity Markers

3β-Methoxy-pregnenolone (MAP4343) as an innovative therapeutic approach for depressive disorders

Assessment of Depression in a Rodent Model of Spinal Cord Injury

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