Sex and age specific effects on auditory brainstem responses in the valproic acid induced rat model of autism

Abstract

[EN]Prenatal exposure to valproic acid (VPA) provides a well-established rodent model of autism, yet its effects on auditory brainstem/midbrain processing across sex and development remain elusive. We recorded click-evoked auditory brainstem responses (ABRs) in Long–Evans rats that received prenatal VPA (400 mg/kg, gestational day 12) and in matched controls at prepubertal (postnatal days 30–45) and adult (65–120) stages under urethane anesthesia. We analyzed peak amplitudes, latencies, inter-peak intervals, and amplitude ratios across sound levels. Auditory thresholds remained comparable among groups. In controls, females showed larger amplitudes for waves I–II, shorter latencies for waves I, II, and IV, and steeper amplitude–intensity slopes for waves II, III, and V than males, indicating stronger level-dependent recruitment. Maturation enhanced early brainstem and midbrain responses by increasing amplitude growth (wave II) and shortening latencies (waves II–V), with effects more pronounced in females. Prenatal VPA exposure reduced wave II amplitude and delayed early peaks (I–III) in females, accompanied by elevated amplitude ratios, whereas in males it mainly affected later responses by reducing amplitudes for waves III–V and prolonging inter-peak latencies (I–III, III–V). These findings show that sex, age, and prenatal VPA exposure distinctly shape auditory brainstem/midbrain function.