The serotonin (5-hydroxytryptamine) 5-HT 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-HT agonist administration on voiding function in the urethane-anesthetised rat, and the change in 5-HT receptor (5-HT R) 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-HT R-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-HT R antagonist, SB-269970 (10 μg/kg), partially reversed LP44-induced changes. Using PRV retrograde tracing and immunofluorescence, 5-HT Rs 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-HT Rs in the ventral L6-S1 spinal cord in SCI rats.

CONCLUSION

A 5-HT R agonist, given i.t., improved voiding efficiency in urethane-anesthetised SCI rats, and the 5-HT R was significantly up-regulated in the lumbosacral cord Onuf's nucleus. If valid for humans, these findings suggest that the 5-HT R could be a target for therapeutic interventions.