title: Effect of 5-HT7 receptor agonist, LP-211, on micturition following spinal cord injury in male rats.
abstract: OBJECTIVE
  Central and peripheral 5-hydroxytryptamine (5-HT) receptors play a critical role in regulation of micturition reflex. The aim of this study was to evaluate effect of a 5-HT7 receptor agonist, LP-211 (N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide) on micturition reflex in acute spinal cord-injured (SCI) rats during infusion of vehicle into the bladder.
  
  
  METHODS
  SCI was induced by compressing T10 segment using an aneurysm clip, extradurally in male rats. Following two weeks, LP-211 doses (0.003-0.3 mg/kg) were administered cumulatively (intraperitoneally, i.p.) with 20 min interval. The 5-HT7 antagonist, SB-269970 ((R)-3-[2-[2-(4-Methylpiperidin-1-yl) ethyl] pyrrolidine-1-sulfonyl] phenol hydrochloride), was administered after achievement of LP-211 dose-response. A cystometric study was performed 2 weeks after spinal crushing in all the animals. Cystometric variables consisting of micturition volume (voided volume), residual volume (volume remaining in the bladder after voiding), and bladder capacity (micturition volume plus residual volume). Voiding efficiency was calculated as the percent of micturition volume to bladder capacity.
  
  
  RESULTS
  Intact and sham-operated rats showed few significant changes in micturition reflex. SCI rats responded to LP-211 (0.003-0.3, mg/kg, i.v.) with dose-dependent increases in bladder capacity, and residual volume. In this treatment group, LP-211 induced significant dose-dependent increases in micturition volume, resulting in significant increases in voiding efficiency (P<0.001) compared to intact and sham-operated rats, SB-269970 (0.1 mg/kg, i.v.) completely reversed the LP-211-induced changes on micturition volume and voiding efficiency was decreased significantly.
  
  
  CONCLUSIONS
  The 5-HT7 receptors activation by LP-211 facilitated the micturition reflex. Furthermore, 5-HT7 receptors do seem to play an important role in physiological regulation of micturition, and as a result, may represent a new strategy to improve voiding efficiency after SCI in patients in the future perspective.
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Norouzi-Javidan
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Javanbakht
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences Tehran, Iran.
authors.forename: Fardin
authors.initials: F
authors.lastname: Barati
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Fakhraei
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mohammadi
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical SciencesTehran, Iran; Experimental Medicine Research Center, School of Medicine, Tehran University of Medical SciencesTehran, Iran; Department of Pharmacology, School of Medicine, Tehran University of Medical SciencesTehran, Iran.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
keywords: 5-HT7; LP-211; Spinal cord injury; micturition; rat