Activation of the external urethral sphincter central pattern generator by a 5-HT1A receptor agonist in rats with chronic spinal cord injury

Paul C. Dolber, Baojun Gu, Xiaoyang Zhang, Matthew O. Fraser, Karl B. Thor, Jerome P. Reiter

    Research output: Contribution to journalArticlepeer-review

    50 Scopus citations


    We recently demonstrated that treatment with the 5-HT1A/7 receptor agonist [(R)-(+)-8-hydroxy-2-di-n-propylamino]tetralin (8-OH-DPAT) increases bladder capacity in chloralose-anesthetized female cats with chronic spinal cord injury. In the current study, we investigated the effects of 8-OH-DPAT on bladder capacity and external urethral sphincter (EUS) activity in urethane-anesthetized female rats (initial body mass 175-200 g) with chronic spinal cord injury (transsection at T10). Cystometric study took place 8-12 wk posttranssection. Intravesical pressure was monitored in urethane-anesthetized rats with a transvesical catheter, and EUS activity was assessed electromyographically. Spinal cord injury disrupts phasic activity of the EUS, resulting in decreased voiding efficiency and increased residual volume. 8-OH-DPAT induced a dose-dependent decrease in bladder capacity (the opposite of its effect in chronic spinal cord-injured cats) with an increase in micturition volume and decrease in residual volume resulting from improvement in voiding efficiency. The unexpected improvement in voiding efficiency can be explained by the 8-OH-DPAT-induced emergence of phasic EUS relaxation. Phasic EUS relaxation was also altered by 8-OH-DPAT in spinally intact rats, whereas the 5-HT 1A receptor antagonist N-tert-butyl-3-[4-(2-methoxyphenyl)-piperazin- 1-yl]-2-phenylpropanamide (WAY-100635), on its own, was without effect. It remains to be determined when phasic relaxation is restored after spinal cord injury, and indeed whether it is ever truly lost or is only temporarily separated from excitatory input.

    Original languageEnglish (US)
    Pages (from-to)R1699-R1706
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Issue number4
    StatePublished - Apr 2007


    • Bladder
    • Detrusor
    • Micturition
    • Neurogenic voiding
    • Urethra

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)


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