Cross-comparison of anesthetic regimens for auditory brainstem response recordings in rats

Auditory brainstem response (ABR) recordings are widely used in neuroscience as a cross-species translational tool to evaluate hearing sensitivity and auditory processing. In animal models, ABR recordings typically require the use of anesthesia to minimize myogenic artifacts, necessitating the development of anesthetic regimens that balance safety, adequate immobilization, and preservation of neural responses. Using a within-subject design in male and female Long-Evans rats, this study systematically evaluated the safety and auditory signal fidelity of five anesthetic regimens -ketamine/xylazine (K/X), ketamine/dexmedetomidine (K/D), dexmedetomidine alone (DEX), dexmedetomidine plus low dose (0.5%) isoflurane (D/I), and high dose (2%) isoflurane (ISO). Anesthetic safety and efficacy were assessed by induction time, recovery time, blood oxygen saturation (SpO₂), and survival rate. ABR signal quality was quantified by threshold, signal strength, wave amplitude, wave latency, and inter-trial phase coherence. K/X anesthesia produced ABRs with low thresholds and well-defined waveforms, but also exhibited the least favorable safety profile, with prolonged recovery times and reduced survival rates. Conversely, isoflurane regimens (ISO and D/I) had a favorable safety profile but significantly elevated thresholds and degraded ABR signal quality, even at low doses. K/D and DEX achieved survival and recovery outcomes equal to or better than conventional anesthetics (K/X and ISO) while also preserving ABR waveform morphology and trial-to-trial reliability. Together, these results highlight dexmedetomidine, particularly when combined with ketamine, as a safe and effective anesthetic for ABR recordings that preserves key metrics of auditory sensitivity and signal integrity.