title: Involvement of purinergic neurotransmission in ketamine induced bladder dysfunction.
abstract: OBJECTIVE
  Long-term ketamine abuse in humans causes significant lower urinary tract symptoms. However, the etiology of ketamine associated cystitis is still not clear. We created a mouse model of ketamine induced lower urinary tract dysfunction to explore the pathogenesis of this condition.
  
  
  METHODS
  Female C57BL/6 mice randomly distributed into control and ketamine groups received daily intraperitoneal injection of saline and ketamine (100 mg/kg), respectively. Cystometry was done in each group at 4, 8 and 16 weeks. After sacrifice the bladders were harvested for isometric muscle tension recording and immunohistochemical examination.
  
  
  RESULTS
  After 8 weeks of treatment body weight growth was significantly decreased in ketamine treated mice. Cystometry revealed a significantly decreased intercontraction interval (mean±SEM 237±9 vs 360±20 seconds, p<0.001) and decreased bladder capacity (0.1±0.004 vs 0.13±0.006 ml, p<0.001) in ketamine vs saline injected mice. Increased adenosine triphosphate evoked detrusor contraction developed in the ketamine group. Immunohistochemical examination revealed increased P2X1 receptor expression in ketamine treated mouse bladders while M2 and M3 receptor expression was unchanged.
  
  
  CONCLUSIONS
  At 8 weeks mice treated with ketamine showed increased voiding frequency and decreased bladder capacity, the same symptoms that develop in human ketamine abusers. Enhanced noncholinergic contractions and P2X1 receptor expression in the ketamine bladder indicate that dysregulation of purinergic neurotransmission may underlie detrusor overactivity in cases of ketamine induced bladder dysfunction.
authors.affiliation: Division of Urology, Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: En
authors.initials: E
authors.lastname: Meng
authors.forename: Han-Yu
authors.initials: HY
authors.lastname: Chang
authors.forename: Sun-Yran
authors.initials: SY
authors.lastname: Chang
authors.forename: Guang-Huan
authors.initials: GH
authors.lastname: Sun
authors.forename: Dah-Shyong
authors.initials: DS
authors.lastname: Yu
authors.forename: Tai-Lung
authors.initials: TL
authors.lastname: Cha
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007649:Ketamine / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D001745:Urinary Bladder Diseases / Q000139:chemically induced*
chemical_list: D011983:Receptors, Purinergic; D007649:Ketamine