SEVERITY ASSESSMENT IN RAT MODELS OF PARKINSON’S DISEASE: INSIGHTS FROM HEART RATE, ACTIVITY, AND BODY WEIGHT MONITORING

Severity assessment is essential in animal experimentation for legal and ethical reasons. The 6-hydroxydopamine (6-OHDA) rat model of Parkinson’s disease is widely used in two variants: bilateral lesions, and unilateral lesions followed by daily levodopa injections to induce dyskinesia. Both models may include intracranial electrode implantation for deep brain stimulation or neuronal recordings. While body weight (BW) is commonly used for severity assessment, continuous monitoring of heart rate (HR) and activity (ACT) may provide additional insight. Male Sprague Dawley rats (n=22) received subcutaneous telemetry transmitters under general anesthesia with analgesia and underwent unilateral intranigral or bilateral intrastriatal 6-OHDA injection, or sham surgery. After three weeks, unilaterally lesioned rats received daily levodopa for 21 days. BW, HR, and ACT were monitored perioperatively and during treatment. A BW deviation index compared postoperative BW with values extrapolated from a preoperative growth curve. HR and ACT were analyzed during nocturnal hours and within ±4 h of levodopa administration. Bilateral 6-OHDA lesions caused transient BW loss relative to expected growth, whereas unilaterally lesioned and control animals followed normal growth trajectories. Both lesion types transiently increased HR and reduced ACT, normalizing within two weeks. Electrode implantation markedly increased HR without affecting BW or ACT. Levodopa transiently increased HR and ACT after injection; nocturnal HR increased at the end of the levodopa treatment period in lesioned animals compared to controls. Overall, both lesion types induced comparable, transient impacts on rat wellbeing. Importantly, BW alone underestimated the impact of electrode implantation, which was detected by HR/ACT monitoring.