Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6‐hydroxydopamine (6‐OHDA) lesion of the nigrostriatal pathway

• Naoki Yoshimura

• Sadako Kuno

• Michael B Chancellor

• William C de Groat

• Satoshi Seki

抄録

<jats:list list-type="explicit-label"> This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6‐OHDA injection into the substantia nigra pars compacta. In 6‐OHDA‐lesioned rats, voided volume per micturition (0.41±0.04 ml, mean±s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham‐operated rats (0.67±0.07 ml). Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46±0.03 ml) in 6‐OHDA‐lesioned rats than in sham rats (0.72±0.06 ml). SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6‐OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6‐OHDA‐lesioned rats and by a smaller increment in sham rats. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6‐OHDA‐lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6‐OHDA‐lesioned rats. PD128907 (D 3 ‐receptor agonist) did not have significant effects on BC in 6‐OHDA‐lesioned rats. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD. British Journal of Pharmacology (2003) 139 , 1425–1432. doi:<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" xlink:href="10.1038/sj.bjp.0705388">10.1038/sj.bjp.0705388

収録刊行物

• British Journal of Pharmacology

  British Journal of Pharmacology 139 (8), 1425-1432, 2003-08

  Wiley

キーワード

• Pharmacology

詳細情報

• CRID: 1362262943584887552
• NII論文ID: 30022966361
• DOI: 10.1038/sj.bjp.0705388
• ISSN: 14765381
• ISSN: 00071188
• Web Site: https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1038%2Fsj.bjp.0705388
• Web Site: https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1038/sj.bjp.0705388
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