Cysteamine Potentiates the Anti-Depressive Effects of Venlafaxine in Corticosterone-Induced Anxiety/Depression Mouse Model: Effect on Brain-Derived Neurotrophic Factor and Tropomyosin-Related Kinase B

The hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been linked to the occurrence of severe depressive and anxiety states. Venlafaxine, a serotonin and a noradrenaline reuptake inhibitor (SNRI), is an approved antidepressant agent with evidence of non-response to treatment in a subset of patients. In this study, 48 male mice (30-38 g) were used to evaluate the possible anxiolytic and antidepressant influence of intraperitoneal (i.p.) cysteamine (150 mg/kg/day) on i.p. venlafaxine (10mg/Kg and 20mg/Kg), as well as effects on brain-derived neurotrophic factor (BDNF) level and tropomyosin-related kinase B (TrkB) gene expression in prefrontal cortex (PFC) in corticosterone-induced anxiety/depression mouse model. The present results provided evidence on insufficient venlafaxine anxiolytic and antidepressant effects in this model. However, cysteamine combined with venlafaxine caused significant antidepressant behavioral effects together with a significant increase in BDNF levels followed by TrkB receptor downregulation in mice PFC. In conclusion, we highlight the potential use of a combination therapy of venlafaxine and cysteamine as a therapeutic strategy for glucocorticoid-related symptoms of depression.