Quantitative Behavioral Method for Assessing Pharmacologically-Induced Episodes of Micturition in an Animal Model of Urinary Retention and Detrusor-Sphincter Dyssynergia

Abstract

No cure or acceptable treatment exists against bladder problems and urinary retention in spinal cord-injured (SCI) patients. Although some non-central nervous system (CNS)-acting drugs exist, as symptomatic treatment, most have been associated with significant side effects and deleterious complications. To ease basic research aimed at identifying new drug candidates against bladder control problems, we develop a standardized approach and corresponding assays for assessing quantitatively acute recovery of bladder expression and episodic urination elicited by CNS-acting compounds in paraplegic animals. Following a period of acclimation, a single systemic (s.c.) injection of vehicle (sterile water) was performed in intact animals or in early chronic (7-10 days post-surgery) thoracically (Th9/10)-transected (Tx) mice. Observations were immediately conducted during 30 minutes using a transparent circular Plexiglas arena where timing (post-injection), frequency (number of episodes post-injection), incidences and total volumes (mg) of expulsed urine were assessed. In clear contrast, administration of quipazine, a 5-HT2/3 receptor agonist was shown here to elicit increased urine volume expressed within 30 min post-administration in Tx mice. Using this simple, straightforward and reliable method, it will become possible to conduct large scale drug screening experiments aimed at identifying potent and safe centrally acting-drugs (e.g., upon the Sacral/Spinal Micturition Center) for potent ‘on-demand’ facilitation of urination and voiding in patients with SCI.