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.
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