Lori Birder led the review process.
Original Basic Science Article
Article first published online: 20 JUL 2011
Copyright © 2011 Wiley Periodicals, Inc.
Neurourology and Urodynamics
Volume 31, Issue 1, pages 168–173, January 2012
How to Cite
Gu, B., Wu, G., Si, J., Xu, Y. and Andersson, K.-E. (2012), Improving voiding efficiency in the diabetic rat by a 5-HT1A serotonin receptor agonist. Neurourol. Urodyn., 31: 168–173. doi: 10.1002/nau.21182
Conflict of interest: none.
- Issue published online: 23 JAN 2012
- Article first published online: 20 JUL 2011
- Manuscript Accepted: 9 JUN 2011
- Manuscript Received: 6 APR 2011
- National Natural Science Foundation of China. Grant Number: 30872568
- Science and Technology Commission of Shanghai Municipality. Grant Number: 09QH1402000
- 5-HT1A receptors;
- diabetic rat;
- external urethral sphincter;
Serotonin affects micturition in the normal rat through actions not only on ascending and descending spinal pathways and supraspinal centers but also on the lumbosacral spinal cord level. The selective 5-HT1A receptor agonist, 8-OH-DPAT((R)-(+)-8-hydroxy-2-(di-n-propylamino) tetralin), reversed detrusor-sphincter dyssynergia (DSD) in the spinal cord injury (SCI) rat. Rats with experimental diabetes mellitus (DM) have been shown to have both bladder and urethral dysfunction during reflex voiding. We therefore examined the effects of 8-OH-DPAT on micturition in DM rats.
Female Sprague–Dawley rats were used. DM was induced by an intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and a cystometric study was performed 8 weeks post-injection. External urethral sphincter electromyography (EUS-EMG) was also measured. The 5-HT1A antagonist WAY-100635(N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) was administered after each 8-OH-DPAT dose–response.
Compared to controls, DM rats had a higher bladder capacity, residual volume, and a lower voiding efficiency. In DM rats, 8-OH-DPAT (3–1,000 µg/kg, i.v.) induced significant dose-dependent increases in micturition volume, and decreases in residual volume, resulting in increases in voiding efficiency. During the micturition, there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency. WAY-100635 (300 µg/kg, i.v.) reversed the 8-OH-DPAT-induced changes.
Both the bladder voiding efficiency and the periodic EUS activity were decreased in DM rats. 5-HT1A receptor agonism promoted periodic EUS activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in DM patients remains to be studied. Neurourol. Urodynam. 31:168–173, 2012. © 2011 Wiley Periodicals, Inc.