Serotonin (5-HT)2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride (DOI) improves voiding efficiency in the diabetic rat.

Objectives To examine the effects of the serotonin (5- HT) 2A/2C receptor agonist (2,5-dimethoxy-4-idophenyl)-2-aminopropane hydrochloride ( DOI) on micturition in rats with diabetes mellitus ( DM). Methods Female Sprague- Dawley rats ( n = 16) were divided into two groups: rats with Type 1 DM and age-matched control rats. DM was induced by i.p. injection of streptozotocin (65 mg/kg) and detailed cystometrogram ( CMG) studies were performed 8 weeks post-injection in all rats under urethane anaesthesia. The selective 5- HT2A antagonist ketanserin was administered after each DOI dose-response curve was plotted. All drugs were administered i.v. Results Compared with controls, comprehensive urodynamic studies showed that DM rats had a higher bladder capacity and post-void residual urine volume ( PVR), and a markedly lower voiding efficiency. In DM rats, DOI (0.01-0.3 mg/kg) induced significant dose-dependent increases in micturition volume and reductions in PVR, resulting in greater voiding efficiency. CMG measurements showed a dose-dependent increase in high-frequency oscillation ( HFO) activity, evidenced by an increased duration of HFOs per voiding. This correlated with the improved voiding efficiency. Ketanserin (0.1 mg/kg) partially or completely reversed the DOI-induced changes. Conclusions The HFOs observed in the present study seem to correlate with external urethral sphincter bursting activity during voiding. Bladder voiding efficiency was reduced in DM rats. The 5- HT2A receptor agonist can enhance HFO activity and improves voiding efficiency, and so may represent a new strategy to improve voiding efficiency after DM in experimental studies. [ABSTRACT FROM AUTHOR]