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

Inge Steuer

Laval University Medical Center (CHU de Québec – CHUL), 2705 Laurier Boulevard, RC-9800 (Neuroscience), Québec City, QC, G1V 4G2, Canada

Magali Grob

Laval University Medical Center (CHU de Québec – CHUL), 2705 Laurier Boulevard, RC-9800 (Neuroscience), Québec City, QC, G1V 4G2, Canada.

Pierre A. Guertin *

Laval University Medical Center (CHU de Québec – CHUL), 2705 Laurier Boulevard, RC-9800 (Neuroscience), Québec City, QC, G1V 4G2, Canada and Department of Psychiatry and Neurosciences, Laval University, Pavillon Vandry, bureau 4873, Québec (Québec) G1V 0A6, Canada

*Author to whom correspondence should be addressed.


Abstract

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.

Keywords: Paraplegia, spinal cord injury, transaction, voiding, bladder problems, rodents, mice


How to Cite

Steuer, Inge, Magali Grob, and Pierre A. Guertin. 2015. “Proof-of-Concept of Acute Drug-Elicited Defecatory Behaviors in Spinal Cord-Transected Animals: A Model for Identifying Centrally-Acting Prokinetic Agents”. Journal of Advances in Medicine and Medical Research 11 (5):1-7. https://doi.org/10.9734/BJMMR/2016/19033.

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