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Involvement of Purinergic Neurotransmission in Ketamine Induced Bladder Dysfunction

2011; Lippincott Williams & Wilkins; Volume: 186; Issue: 3 Linguagem: Inglês

10.1016/j.juro.2011.04.102

1527-3792

En Meng, Han-Yu Chang, Sun‐Yran Chang, Guang‐Huan Sun, Dah‐Shyong Yü, Tai‐Lung Cha,

Stress Responses and Cortisol

No AccessJournal of UrologyInvestigative Urology1 Sep 2011Involvement of Purinergic Neurotransmission in Ketamine Induced Bladder Dysfunction En Meng, Han-Yu Chang, Sun-Yran Chang, Guang-Huan Sun, Dah-Shyong Yu, and Tai-Lung Cha En MengEn Meng , Han-Yu ChangHan-Yu Chang , Sun-Yran ChangSun-Yran Chang , Guang-Huan SunGuang-Huan Sun , Dah-Shyong YuDah-Shyong Yu , and Tai-Lung ChaTai-Lung Cha View All Author Informationhttps://doi.org/10.1016/j.juro.2011.04.102AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: 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. Materials and 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. References 1 Anti-Drug Report 2010. Taiwan, Republic of China: Ministry of Justice, Ministry of Education and Ministry of Foreign Affairs2010. Google Scholar 2 : Adapting the Illicit Drug Reporting System (IDRS) to examine the feasibility of monitoring trends in the markets for 'party drugs'. Drug Alcohol Depend2004; 73: 189. Google Scholar 3 : Patterns of use and harms associated with non-medical ketamine use. Drug Alcohol Depend2003; 69: 23. Google Scholar 4 : Club drugs: methylenedioxymethamphetamine, flunitrazepam, ketamine hydrochloride, and gamma-hydroxybutyrate. 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Volume 186Issue 3September 2011Page: 1134-1141 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.Keywordsmiceketaminereceptors, purinergicurinary bladdersubstance-related disordersAcknowledgmentsDr. J. S. Young critically read the manuscript.MetricsAuthor Information En Meng More articles by this author Han-Yu Chang More articles by this author Sun-Yran Chang More articles by this author Guang-Huan Sun More articles by this author Dah-Shyong Yu More articles by this author Tai-Lung Cha More articles by this author Expand All Advertisement PDF downloadLoading ...