Serotonergic drugs and spinal cord transections indicate that different spinal circuits are involved in external urethral sphincter activity in rats

Am J Physiol Renal Physiol. 2007 Mar;292(3):F1044-53. doi: 10.1152/ajprenal.00175.2006. Epub 2006 Oct 17.

Abstract

Lower urinary tract function is regulated by spinal and supraspinal reflexes that coordinate the activity of the urinary bladder and external urethral sphincter (EUS). Two types of EUS activity (tonic and bursting) have been identified in rats. This study in urethane-anesthetized female rats used cystometry, EUS electromyography, spinal cord transection (SCT) at different segmental levels, and analysis of the effects of 5-HT(1A) receptor agonist (8-OH-DPAT) and antagonist (WAY100635) drugs to examine the origin of tonic and bursting EUS activity. EUS activity was elicited by bladder distension or electrical stimulation of afferent axons in the pelvic nerve (pelvic-EUS reflex). Tonic activity evoked by bladder distension was detected in spinal cord-intact rats and after acute and chronic T8-9 or L3-4 SCT but was abolished after L6-S1 SCT. Bursting activity was abolished by all types of SCT except chronic T8-9 transection. 8-OH-DPAT enhanced tonic activity, and WAY100635 reversed the effect of 8-OH-DPAT. The pelvic-EUS reflex consisted of an early response (ER) and late response (LR) when the bladder was distended in spinal cord-intact rats. ER remained after acute or chronic T8-9 and L3-4 SCT, but was absent after L6-S1 SCT. LR occurred only in chronic T8-9 SCT rats where it was enhanced or unmasked by 8-OH-DPAT. The results indicate that spinal serotonergic mechanisms facilitate tonic and bursting EUS activity. The circuitry for generating different patterns of EUS activity appears to be located in different segments of the spinal cord: tonic activity at L6-S1 and bursting activity between T8-9 and L3-4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Electric Stimulation
  • Electromyography
  • Female
  • Hydrostatic Pressure
  • Infusions, Parenteral
  • Models, Neurological
  • Muscle Contraction / drug effects
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiopathology*
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reflex / drug effects
  • Serotonin Agents / pharmacology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Spinal Cord Injuries / physiopathology*
  • Spinal Nerves / drug effects
  • Spinal Nerves / physiopathology*
  • Urethra / drug effects
  • Urethra / innervation
  • Urethra / physiopathology*
  • Urinary Bladder / drug effects
  • Urinary Bladder / innervation
  • Urinary Bladder / physiopathology
  • Urination / drug effects

Substances

  • Piperazines
  • Pyridines
  • Serotonin Agents
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin