Dopaminergic urethral closure mechanisms in a rat model of Parkinson's disease. Issue 5 (1st April 2019) - Ouchi, Mifuka
Abstract: Aims: Urinary incontinence is prevalent among patients with Parkinson's disease (PD). In the present study, we investigated urethral functions in a rat model of PD induced by 6‐hydroxydopamine injection at their substantia nigra pars compacta as well as the roles of selective agonists/antagonist of dopamine D1‐ and D2‐like receptors in active urethral closure mechanisms. Methods: We measured changes in the urethral pressure amplitude during electrical stimulation, urethral baseline pressure, and leak point pressure after intravenous administration of selective agonists or antagonists of the dopamine D1‐ and D2‐like receptors in a rat model of PD. Results: The mean leak point pressure and the mean active urethral response values were significantly smaller for the untreated PD rat group compared with the control group. In PD model, the active urethral response increased significantly after treatment with the dopamine D1‐like receptor agonist, whereas that induced by the dopamine D2‐like receptor agonist decreased significantly. The response to the D2‐like receptor agonist was suppressed in the PD rat by the dopamine D2‐like receptor antagonist. Conclusion: Our results suggest that the active urethral closure mechanisms are significantly impaired when dopamine is depleted. In the PD rat, dopamine D1‐like receptor activity on the central nervous system appear to partially compensate for urethral functions negatively impacted by the lack of dopamine, whereas dopamine D2‐like receptor activity might exacerbate urinary leakage owing to the negative effect of this activated receptor on urethral pressure under increased intra‐abdominal pressure.