Fluoxetine, a selective serotonin reuptake inhibitor used clinically, improves bladder function in a mouse model of moderate spinal cord injury

Abstract

After spinal cord injury, the upward conduction of the spinal cord is lost, resulting in the loss of micturition control, which manifests as detrusor sphincter dyssynergia and insufficient micturition. Studies have shown that serotonergic axons play important roles in the control of the descending urination tract. In this study, mouse models of moderate spinal cord contusions were established. The serotonin agonists quipazine (0.2 mg/kg), 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DAPT, 0.1 mg/kg), buspirone (1 mg/kg), sumatriptan (1 mg/kg), and rizatriptan (50 mg/kg), the serotonin reuptake inhibitors fluoxetine (20 mg/kg) and duloxetine (1 mg/kg), and the dopamine receptor agonist SKF-82197 (0.1 mg/kg) were intraperitoneally administered to the model mice 35 days post-injury in an acute manner. The voided stain on paper method and urodynamics revealed that fluoxetine reduced the amount of residual urine in the bladder and decreased bladder and external urethral sphincter pressure in a mouse model of moderate spinal cord injury. However, fluoxetine did not improve the micturition function in a mouse model of severe spinal cord injury. In contrast, the other serotonergic drugs had no effects on the micturition functions of spinal cord injury model mice. This study was ethically approved by the Institutional Animal Care and Use Committee of Jiangsu Province Hospital of Chinese Medicine (approval No. 2020DW-20-02) on September 11, 2020.

Keywords

• bladder; external urethral sphincter; fluoxetine; micturition; selective serotonin reuptake inhibitor; spinal cord injury; urodynamics; voided stain on paper measurement