Effect of chronic citalopram on serotonin-related and stress-regulated genes in the dorsal raphe nucleus of the rat
Using a model of depression in which chronic social stress induces depressive-like symptoms, we investigated effects of the selective serotonin-reuptake inhibitor (SSRI) citalopram on gene expression in the dorsal raphe nucleus of male rats. Expression of tryptophan hydroxylase (TPH) protein was found to be upregulated by the stress and normalized by citalopram, while mRNAs for genes TPH 1 and 2 were differentially affected. Citalopram had no effect on serotonin transporter mRNA but reduced serotonin-1A autoreceptor mRNA in stressed animals. The SSRI prevented the stress-induced upregulation of mRNA for CREB binding protein, synaptic vesicle glycoprotein 2b and the glial N-myc downstream-re…
Chronic social stress inhibits cell proliferation in the adult medial prefrontal cortex: hemispheric asymmetry and reversal by fluoxetine treatment.
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 proliferatio…
Effects of escitalopram on the regulation of brain-derived neurotrophic factor and nerve growth factor protein levels in a rat model of chronic stress.
Escitalopram (ES-CIT) is a widely used, highly specific antidepressant. Until now there has been very little evidence on how this drug under pathological conditions affects an important feature within the pathophysiology of stress-related disorders such as depression: the endogenous neurotrophins. By using a well-characterized rat model in which chronic stress induces depressive-like behavior, the levels of neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were determined in representative brain regions and serum using a highly sensitive improved fluorometric two-site ELISA system. There was a significant increase of BDNF in the left and right cortices aft…
Effects of fluoxetine on behavioral deficits evoked by chronic social stress in rats.
Recently, we described an advanced model of chronic social stress in male rats based on the resident intruder paradigm. In this model, rats subjected to daily social stress for 5 weeks showed behavioral changes resembling anhedonia and motivational deficits in humans. In the present study, male Wistar rats were subjected to 5 weeks of daily social defeat by an aggressive conspecific and concomitant treatment with the antidepressant drug fluoxetine (10 mg/kg) after the first week of stress. Compared with controls, rats exposed to chronic stress had significantly reduced locomotor and exploratory activity (rearing and sniffing) and diminished preference for sucrose solution. These effects wer…