title: Improving voiding efficiency in the diabetic rat by a 5-HT1A serotonin receptor agonist.
abstract: OBJECTIVE
  Serotonin affects micturition in the normal rat through actions not only on ascending and descending spinal pathways and supraspinal centers but also on the lumbosacral spinal cord level. The selective 5-HT1A receptor agonist, 8-OH-DPAT((R)-(+)-8-hydroxy-2-(di-n-propylamino) tetralin), reversed detrusor-sphincter dyssynergia (DSD) in the spinal cord injury (SCI) rat. Rats with experimental diabetes mellitus (DM) have been shown to have both bladder and urethral dysfunction during reflex voiding. We therefore examined the effects of 8-OH-DPAT on micturition in DM rats.
  
  
  METHODS
  Female Sprague-Dawley rats were used. DM was induced by an intraperitoneal injection of streptozotocin (STZ, 65 mg/kg) and a cystometric study was performed 8 weeks post-injection. External urethral sphincter electromyography (EUS-EMG) was also measured. The 5-HT1A antagonist WAY-100635(N-tert-butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide) was administered after each 8-OH-DPAT dose-response.
  
  
  RESULTS
  Compared to controls, DM rats had a higher bladder capacity, residual volume, and a lower voiding efficiency. In DM rats, 8-OH-DPAT (3-1,000 µg/kg, i.v.) induced significant dose-dependent increases in micturition volume, and decreases in residual volume, resulting in increases in voiding efficiency. During the micturition, there was a dose-dependent increased phasic EUS activity correlated with the improved voiding efficiency. WAY-100635 (300 µg/kg, i.v.) reversed the 8-OH-DPAT-induced changes.
  
  
  CONCLUSIONS
  Both the bladder voiding efficiency and the periodic EUS activity were decreased in DM rats. 5-HT1A receptor agonism promoted periodic EUS activity, thereby improving voiding efficiency. Whether or not these results may have implications for the future treatment of voiding dysfunction in DM patients remains to be studied.
authors.affiliation: Department of Urology, Shanghai 6th People's Hospital, Shanghai Jiaotong University, Shanghai, People's Republic of China. gubaojun@yahoo.com
authors.forename: Baojun
authors.initials: B
authors.lastname: Gu
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
authors.forename: Jieming
authors.initials: J
authors.lastname: Si
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Xu
authors.forename: Karl-Erik
authors.initials: KE
authors.lastname: Andersson
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004576:Electromyography; D005260:Female; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D013311:Streptozocin / Q000009:adverse effects; D014521:Urethra / Q000187:drug effects* / Q000503:physiopathology; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D014554:Urination / Q000187:drug effects* / Q000502:physiology*; D014556:Urine / Q000502:physiology
chemical_list: D010879:Piperazines; D011725:Pyridines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D013311:Streptozocin; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin