Acute nicotine affects auditory brainstem responses in a frequency-, age-, and sex-dependent manner in mice

Age-related hearing loss (presbycusis) is a widespread sensory disorder associated with diminished quality of life and increased risk of cognitive decline, with limited treatment options. While nicotinic acetylcholine receptor modulation is a potential treatment for improving auditory function, it is unclear if nicotine affects auditory responses in an age- and sex-dependent manner. To test this, we recorded tone-evoked auditory brainstem responses (ABR) from young (2-3 months) and old (16-22 months) male and female mice (FVB strain) following an injection of saline or nicotine (0.5 mg/kg, i.p.). We analyzed hearing threshold and ABR wave amplitudes putatively corresponding to activity in the auditory nerve (wave I), lateral lemniscus (wave IV), and inferior colliculus (wave V). We found age-related reduction in hearing sensitivity and ABR wave amplitudes across frequency. We found sex differences in a frequency- and ABR wave-specific manner, with old females showing a greater loss in hearing sensitivity and wave I amplitude compared to old males. Nicotine improved hearing sensitivity at high frequencies. Nicotine altered V amplitudes in a sex-, age-, and frequency-dependent manner, but had no significant effect on wave I and IV amplitudes. Together, these findings indicate that nicotine can improve hearing sensitivity and support further investigation of nicotinic acetylcholine receptor-targeting compounds as potential therapy for presbycusis. The FVB mouse strain may provide a useful model to study conditions in which females show a sharper age-related decline in hearing compared to males.