The serotonin (5‐hydroxytryptamine) 5‐HT7 receptor is up‐regulated in Onuf's nucleus in rats with chronic spinal cord injury

Objectives To examine the effect of intrathecal (i.t.) serotonin (5‐hydroxytryptamine) 5‐HT7 agonist administration on voiding function in the urethane‐anesthetised rat, and the change in 5‐HT7 receptor (5‐HT7R) expression in the lumbosacral cord Onuf's nucleus after spinal cord injury (SCI). Materials and methods In all, 32 female Sprague–Dawley (SD) rats were equally divided into a spinally intact (SI) group and SCI group (n = 16 each). At 8 weeks after transection, half of the rats underwent continuous cystometry under urethane anaesthesia, and the 5‐HT7R‐selective agonist LP44 was given (i.t.). The remaining rats were used for pseudorabies (PRV) retrograde tracing, immunofluorescence, and Western Blot. Results LP44 administered i.t. had no effect in the SI rats. In SCI rats, LP44 (1–30 μg/kg) induced significant dose‐dependent increases in micturition volume, voiding efficiency, number of high‐frequency oscillations per micturition; and decreases in residual volume, bladder capacity, peak bladder pressure, threshold pressure and non‐voiding contractions. The 5‐HT7R antagonist, SB‐269970 (10 μg/kg), partially reversed LP44‐induced changes. Using PRV retrograde tracing and immunofluorescence, 5‐HT7Rs were found in the L6–S1 spinal cord Onuf's nucleus in both SI and SCI rats, but the expression was significantly greater in the SCI rats. Western blot showed significantly more 5‐HT7Rs in the ventral L6–S1 spinal cord in SCI rats. Conclusion A 5‐HT7R agonist, given i.t., improved voiding efficiency in urethane‐anesthetised SCI rats, and the 5‐HT7R was significantly up‐regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5‐HT7R could be a target for therapeutic interventions.