Gender-Specific Behavior Reductions in Spontaneous Locomotive and Rearing in a Rat Model of Paclitaxel-Induced Peripheral Neuropathy: A Pilot Study

Introduction: Chemotherapy-induced peripheral neuropathy (CIPN) from agents like paclitaxel causes sensory loss and functional impairment, with limited treatment options. To better model patient-relevant outcomes, we used open field video tracking in rodents to assess gait, anxiety, and exploratory behavior. This approach provides a more comprehensive assessment of CIPN-related deficits beyond pain responses. Methods and Materials: Adult male and female Sprague Dawley rats were given paclitaxel (Taxol; 24 mg/kg cumulative dose) or a vehicle over 8 days. Their distance traveled, time spent in the center and outer zones of the OF test, and rearing behaviors were recorded using a PhenoTyper 4500 OF system before and after treatment. Behavioral outcomes were analyzed using 2-way repeated measures analysis of variance (ANOVA) with significance set at p < 0.05. Results: Paclitaxel treatment significantly reduced locomotor activity and rearing behavior in rats, reflecting functional impairments relevant to human CIPN. A three-way ANOVA revealed sex-specific effects, prompting separate analyses by sex. Taxol-treated males showed marked decreases in both distance traveled and rearing, while females exhibited reductions in locomotion but not rearing. No consistent changes were observed in anxiety-like behavior, highlighting the selective impact of paclitaxel on motor and exploratory functions. Discussion/Conclusion: This pilot study demonstrated that paclitaxel-treated rats exhibited significant reductions in spontaneous behaviors such as distance traveled and rearing activity. These ethologically relevant behavioral measures reflect the clinical symptoms of CIPN in humans and highlight the utility of OF activity as an appropriate method for tracking ongoing pain and treatment efficacy in preclinical models of PIPN. Keywords: chemotherapy-induced peripheral neuropathy, paclitaxel, open field test, locomotor activity, rearing behavior, spontaneous pain behavior, behavioral tracking