Corticotropin-releasing hormone 1 receptor antagonism attenuates chronic unpredictable mild stress-induced depressive-like behaviors in rats.

Hyperactivity of the hypothalamic-pituitary-adrenal axis and impairment of the central corticotropin-releasing factor system are factors in the pathogenesis of depression. Though several antagonists of the corticotropin-releasing factor 1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between corticotropin-releasing factor 1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of CP154526, a corticotropin-releasing factor 1 receptor blocker, which presented some signs of depression. Our results revealed that CP154526 (5 and 10 mg/kg) or fluoxetine (10 mg/kg) treatment notably improved the sucrose consumption, produced anti-depressive-like behavior in open-field test, as well as immobility time in forced swimming test. The levels of interleukin-6, interleukin-1ß, tumor necrosis factor-α, and corticotropin-releasing hormone concentration in the serum were inhibited effectively by CP154526 or fluoxetine administration. Real-time quantitative PCR and western blot analysis showed the upregulated levels of brain-derived neurotrophic factor and growth associated protein 43 (GAP43) in the hypothalamus of the rats exposed to chronic unpredictable mild stress (CUMS), while different degrees of downregulation in their expression were detected after CP154526 (5 and 10 mg/kg) or fluoxetine (10 mg/kg) treatment, respectively. Thus, our data demonstrated that CP154526 exhibited antidepressant effect in CUMS rats, which might be mediated by decreasing the brain-derived neurotrophic factor and GAP43 expression in the hypothalamus.

Ginsenoside Rg1 attenuates chronic unpredictable mild stress-induced depressive-like effect via regulating NF-κB/NLRP3 pathway in rats.

Ginsenoside (GS Rg1), which has neuroprotection and anti-inflammation activities, is the main active ingredient of Radix Ginseng. However, its antidepressant-like effect in rats remains unclear. Our study was conducted to investigate whether GS Rg1 confers an antidepressant effect in rats exposed to a chronic unpredictable mild stress model of depression and to explore its possible mechanisms. Our results revealed that GS Rg1 treatments for 3 weeks alleviated the depression-related behaviors of chronic unpredictable mild stress-exposed rats, as indicated by increasing sucrose preference, improving locomotor activity and shortening immobile time in both the forced swimming tests and tail suspension tests. And these ameliorative effects of GS Rg1 treatment were involved with regulating chronic unpredictable mild stress-induced pro-inflammatory cytokine interleukin beta (IL-1ß) related neuro-inflammation. In addition, we further found that GS Rg1 reversed chronic unpredictable mild stress-induced IL-1ß elevation, possibly by inhibiting nuclear factor kappa B pathway activation and regulating nucleotide binding and oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome expression. In short, our results suggested that GS Rg1 exerted a potential antidepressant-like effect in chronic unpredictable mild stress rat model of depression, which may provide an insight into the potential of GS Rg1 in therapeutic implications for depression.

Effect of Cognitive Behavioral Therapy on Improving the Cognitive Function in Major and Minor Depression.

The aim of this study was to investigate the effectiveness of cognitive behavioral therapy (CBT) on improving the cognitive function in minor depression (MiD) and major depression (MaD). The study will constitute a placebo-controlled single-blind parallel-group randomized controlled trial. The selected participants will be randomly allocated into one of two parallel groups with a 1:1 ratio: the CBT-based group and the general health education group. CBT significantly alleviated depressive symptoms of MiD and MaD at 12 weeks (p < 0.001), and the treatment effect was maintained for at least 12 months (p < 0.001). Interestingly, CBT significantly promotes more cognitive function of MiD and partial cognitive function of MaD at 12 weeks in the intervention group than in the control group (p < 0.01). CBT can alleviate depressive symptoms of both minor and MaDs. The effectiveness of CBT is different on improving the cognitive function in MiD and MaD.