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

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: 10.1038/sj.bjp.0705388