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

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.