Biphasic effect of apomorphine, an anti-parkinsonian drug, on bladder function in rats

• Published in: Neuroscience 2009-09, Vol.162 (4), p.1333-1338
• Main Authors: Uchiyama, T, Sakakibara, R, Yoshiyama, M, Yamamoto, T, Ito, T, Liu, Z, Yamaguchi, C, Awa, Y, Yano, H.-M, Yanagisawa, M, Yamanishi, T, Hattori, T, Kuwabara, S
• Format: Article
• Language: English
• Subjects: Animals; Antiparkinson Agents - adverse effects; apomorphine; Apomorphine - adverse effects; Biological and medical sciences; bladder; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; dopamine; Dopamine Agonists - adverse effects; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; lower urinary tract; Male; Medical sciences; Neurology; Parkinson disease; Rats; Rats, Sprague-Dawley; Urinary Bladder - drug effects; Urinary Bladder - physiology; Urination - drug effects; Urine; urodynamics; Vertebrates: nervous system and sense organs
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2009.06.001

Abstract The effects of anti-parkinsonian drugs on bladder function have been controversial; namely, some aggravated while others alleviated bladder dysfunction in patients with Parkinson disease. These studies, however, did not consider the dose- and time-dependent effects. Therefore, we investigated these effects of apomorphine, an anti-parkinsonian drug and a nonselective dopamine receptor agonist, on the bladder function using normal conscious rats. Consecutive cycles of micturition were analyzed for 30-min periods before and after (over a 4-h period) s.c. administration of a single dose of 0.01 (low), 0.05 (medium), 0.5 (high) mg/kg of apomorphine or saline to the rats. Apomorphine administration produced various effects in relevant urodynamic parameters, although the monitored parameters remained unchanged in saline-administered rats. During filling, low-dose apomorphine induced initial decreases in voiding frequency (VF; defined as the number of voidings during a 15-min period). However, medium- and high-dose apomorphine dose-dependently induced initial increases in VF, and was followed by decreases in VF. These doses also induced initial increase in threshold pressure. During voiding, low-dose apomorphine induced initial increases in micturition volume (MV), which reflected an increase in bladder capacity (BC). However, medium- and high-dose apomorphine dose-dependently induced initial decreases in MV, and was followed by increases in MV. These doses also dose-dependently induced an initial increase in maximum bladder contraction pressure during the early phase after administration. The present study demonstrated that apomorphine displayed a dose- and time-dependent biphasic effect on the normal bladder filling function. These pharmacodynamic characteristics of apomorphine could be applicable to other anti-parkinsonian drugs such as levodopa and nonselective dopamine receptor agonists, and may account for the previous reported conflicting effects of anti-parkinsonian drugs on bladder dysfunction in patients with Parkinson disease, although it needs to be evaluated in disease status.