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

摘要

class="enumerated" style="list-style-type:decimal">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). (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. 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 (D3-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.