Inhibition of Rho kinase by GSK 269962 reverses both corticosterone-induced detrusor overactivity and depression-like behaviour in rats

Abstract Literature data give clear evidence that upregulated RhoA/Rho-kinase signalling is one of the factors that may lead to the development of detrusor overactivity and various disorders of the central nervous system. Therefore, the main objective of our study was to investigate whether administration of a Rho-kinase inhibitor – GSK 269962 could reverse corticosterone-induced depressive-like behaviour and changes in cystometric parameters associated with detrusor overactivity, as well as undo the alterations of several biomarkers related to both disorders (i.e., pro-inflammatory/anti-inflammatory cytokines and neurotrophins) in serum, urinary bladder, and different brain structures. The experiments were carried out on female Wistar rats. Surgical procedures, cystometric investigations, biochemical analyses, and behavioural studies (measurement of the locomotor activity and the forced swim test) were performed according to the published literature. As expected, administration of corticosterone at a daily dose of 20 mg/kg for 14 days increased the immobility time of animals in the forced swim test, induced changes in the cystometric parameters specific to bladder overactivity, reduced levels of neurotrophins, and elevated concentrations of the pro-inflammatory cytokines. Inhibition of Rho-kinase by 7-day treatment with GSK 269962 (10 mg/kg/day) reversed the symptoms of both detrusor overactivity and depression as well as normalized levels of the tested biomarkes. Our findings encourage the idea of Rho-kinase inhibitors as a potential future treatment option for overactive bladder accompanied by depression.