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

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.

Proof-of-Concept of Acute Drug-Elicited Defecatory Behaviors in Spinal Cord-Transected Animals: A Model for Identifying Centrally-Acting Prokinetic Agents.

No cure and no safe or acceptable treatment exist yet against bowel problems and chronic constipation in spinal cord-injured (SCI) patients. Although some non-central nervous system (CNS)-acting drugs have already been identified and used clinically 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 bowel control problems, we developed a standardized approach and corresponding assays for quantitatively measuring prokinetic and acute defecatory effects in paraplegic animals. Following a period of acclimation, a single subcutaneous injection of 0.5 ml of vehicle (sterile water) was performed in normal animals or in early chronic (> 7 days post-surgery) low-thoracically (Th9/10)-transected (Tx) mice. A 30 minute-period of observation of freely moving animals using a transparent Plexiglas arena was used to subsequently measure timing (latency of each episode), amounts (fecal pellets in mg) and frequency (number of episodes/30 min). Residual activity levels, clearly determined in control animals, were used as baseline level to determine statistically greater effects induced by compounds of potential interest. Tests with SR57227 (5-HT3 receptor agonist) and quipazine (5-HT2/3 receptor agonist) revealed that only quipazine acutely elicited significantly greater amounts of fecal pellets in Tx mice. Using this straightforward and reliable method, future drug screening experiments that may yield the identification and development of new potent and safe centrally acting-drug treatments (e.g., upon the Lumbosacral Defecation Center) for potent ‘on-demand’ facilitation or induction of reflex bowel control and acute episodes of defecation in patients with SCI.