Suppression of bladder reflex activity in chronic spinal cord injured cats by activation of serotonin 5-HT1A receptors

Exp Neurol. 2006 Jun;199(2):427-37. doi: 10.1016/j.expneurol.2006.01.007. Epub 2006 Feb 20.

Abstract

The effects of 8-OH-DPAT (5-HT1A receptor agonist) and WAY100635 (5-HT1A receptor antagonist) on reflex bladder activity were investigated in alpha-chloralose anesthetized or conscious chronic spinal cord injured cats. The results were similar in both anesthetized and conscious animals. Cystometrograms revealed that 8-OH-DPAT (0.5 mg/kg, s.c.) significantly increased the bladder volume threshold for eliciting a large amplitude micturition contraction, but only slightly reduced the amplitude of the contractions and did not alter the small amplitude pre-micturition contractions. 8-OH-DPAT also reduced the amplitude of isovolumetric bladder contractions. The inhibitory effect of 8-OH-DPAT was reversed by WAY100635 (0.5 mg/kg) or blocked by pre-treatment with WAY100635. Reflex bladder contractions evoked by tactile stimulation of the perigenital region were not altered by 8-OH-DPAT. These results suggest that the inhibitory effect of 8-OH-DPAT is mediated by an action on interneuronal pathways in the spinal cord or on the C-fiber afferent limb of the spinal micturition reflex and not on bladder smooth muscle or the efferent limb of the reflex pathway. Drugs that activate 5-HT1A receptors might be useful in treating detrusor overactivity after spinal cord injury.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Cats
  • Chronic Disease
  • Disease Models, Animal
  • Female
  • Male
  • Piperazines / pharmacology
  • Pyridines / pharmacology
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Reflex / drug effects
  • Reflex / physiology*
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Spinal Cord Injuries / physiopathology*
  • Urinary Bladder / drug effects
  • Urinary Bladder / physiopathology*
  • Wakefulness

Substances

  • Piperazines
  • Pyridines
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Receptor, Serotonin, 5-HT1A
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • 8-Hydroxy-2-(di-n-propylamino)tetralin