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Am J Physiol Regul Integr Comp Physiol (January 4, 2007). doi:10.1152/ajpregu.00142.2006
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Submitted on February 28, 2006
Accepted on December 20, 2006

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

Paul C Dolber1, Baojun Gu2*, Xiaoyang Zhang3, Matthew Oliver Fraser4, Karl B Thor5, and Jerome P. Reiter6

1 Dept. of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina, United States; Div. of Urology, Dept. of Surgery, Duke University Medical Center, Durham, United States; Dept. of Pathology, Duke University Medical Center, Durham, United States
2 Dept. of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina, United States; Div. of Urology, Dept. of Surgery, Duke University Medical Center, Durham, United States; Shanghai Jiaotong University, Affiliated 6th People, Shanghai, China
3 Dept. of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina, United States; Div. of Urology, Dept. of Surgery, Duke University Medical Center, Durham, North Carolina, United States
4 Dept. of Surgery, Durham Veterans Affairs Medical Center, Apex, North Carolina, United States; Div. of Urology, Dept. of Surgery, Duke University Medical Center, Durham, North Carolina, United States; Urogenics Pharmaceuticals, Inc., United States
5 Dept. of Surgery, Durham Veterans Affairs Medical Center, Durham, North Carolina, United States; Div. of Urology, Dept. of Surgery, Duke University Medical Center, Durham, North Carolina, United States; Div. of Gynecologic Specialities, Dept. of Ob/Gyn, Duke University Medical Center, Durham, North Carolina, United States; Urogenics Pharmaceuticals, Inc., United States
6 Institute of Statistics and Decision Sciences, Duke University, Durham, North Carolina, United States

* To whom correspondence should be addressed. E-mail: gubaojun{at}yahoo.com.

We recently demonstrated that treatment with the 5-HT1A/7 receptor agonist 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 gm) with chronic spinal cord injury (transection at T10). Cystometric study took place 8-12 weeks post-transection. Intravesical pressure was monitored in urethane-anesthetized rats with a transvesical catheter and external urethral sphincter (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-HT1A receptor antagonist 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.




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