The GPR39 Receptor Plays an Important Role in the Pathogenesis of Overactive Bladder and Corticosterone-Induced Depression.

Despite the close and clinically confirmed association between depression and overactive bladder, it remains unclear whether this affective disorder is a factor causing overactive bladder or whether overactive bladder is a specific symptom of psychosomatic disorders. This study examined the effects of repeated corticosterone administration on the occurrence of symptoms associated with depression and overactive bladder. Additionally, we examined whether administering TC-G 1008, an antidepressant that selectively activates the GPR39 receptor, could alleviate corticosterone-induced depression-like behavior and detrusor overactivity-related changes in cystometric measurements. We also explored its potential to reverse alterations in various biomarkers associated with both conditions in the serum, urinary bladder, and brain of female rats. The administration of corticosterone (20 mg/kg/day for 14 days) yielded anticipated results, including an increase in the duration of immobility during the forced swim test, alterations in parameters specific to bladder overactivity, a decrease in neurotrophins, and an elevation in pro-inflammatory cytokine levels. Treatment with TC-G 1008 (15 mg/kg/day) alleviated symptoms of both detrusor overactivity and depression, while also restoring the levels of biochemical and cystometric markers to normal ranges. Additionally, antidepressants based on GPR39 agonists could enhance the levels of kynurenic acid in the neuroprotective pathway. These results indicate that the GPR39 agonist receptor might be a promising future therapeutic approach for treating overactive bladder that occurs alongside depression.