Acute Dose-Related Effect of Antiseizure Medicines on Open Field Exploration of Rats with Established Epilepsy
Abstract number :
1.273
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2023
Submission ID :
338
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Qian Wu, MD, PhD – University of Washington
Dannielle Zierath, B.S. – Research Scientist III, Center for Epilepsy Drug Discovery; Pharmacy, University of Washington; Kevin Knox, B.S. – Research Scientist I, Center for Epilepsy Drug Discovery; Pharmacy, University of Washington; H. Steve White, PhD – Professor, Center for Epilepsy Drug Discovery; Pharmacy, University of Washington; Melissa Barker-Haliski, PhD – Research Associate Professor, Center for Epilepsy Drug Discovery; Pharmacy, University of Washington
Rationale: Antiseizure medicines (ASMs) are associated with behavioral side effects in people with epilepsy, yet ASM discovery typically relies on tolerability profiling in neurologically intact, seizure naïve rodents using subjective behavioral assays such as the Irwin test. Further, the acute dose-related effect of ASMs on behavioral performance in rodents with epilepsy is underreported. This project used the objective, automated open field task (OFT) to quantitate the dose-related effect of acute ASM administration on gross locomotor activity and exploration of post-kainic acid (KA) induced-status epilepticus (SE) rats with epilepsy to pharmacologically differentiate the effects of ASMs on exploratory behavior.
Methods: Male Sprague-Dawley rats (100–125 g on order, Charles River) underwent KA-SE before surgical implantation of video-EEG electrodes two weeks post-SE; rats were observed for the presence of spontaneous recurrent seizures (SRS) for eight to ten weeks post-SE to confirm established epilepsy. Rats with SRS (n=8/group) or age-matched SE-naïve rats (n=6/group) were then acutely challenged with a single, intraperitoneal administration of the median effective dose (ED50) or median behaviorally impairing dose (TD50) of carbamazepine (CBZ) or valproic acid (VPA), before being placed into an automated OFT for quantitative assessment of behavior at the time of peak effect of each ASM. During the 10-min test, total distance traveled (cm), horizontal activity counts, vertical rearing counts, and percentage of time in center zone were recorded. OFT was evaluated by two-way ANOVA, with Tukey’s post hoc test with GraphPad Prism >v.8, p < 0.05 considered significant.
Anti-seizure Medications