Aspartate and glutamate were monitored in the scala tympani of the guinea p
ig cochlea using in vivo microdialysis before and during noise exposure; Mo
derate level broad band noise [105 dB sound pressure level (SPL), 30 min] n
either altered the levels of aspartate or glutamate, nor auditory brainstem
response (ABR) thresholds. High level noise exposure (135 dB SPL, 30 min)
caused a large increase in aspartate (330%), a smaller increase in glutamat
e (150%), and a permanent ABR threshold shift of 60-75 dB between 2.0 and 1
2.5 kHz. Morphological analysis of the cochlea revealed a collapse of suppo
rting structures, swelling of the afferent dendrites under the inner hair c
ells, and outer hair cell loss. Pretreatment with the NMDA antagonist, MK 8
01 (1 mg/kg body weight, i.p.) 1 h before noise exposure protected the affe
rent dendrites from swelling but did not protect the collapse of supporting
structures, outer hair cell loss, or auditory thresholds. In conclusion, t
he noise-induced increase in aspartate and glutamate release in the cochlea
and the protective effect of NMDA antagonism suggest that these two neurot
ransmitters are involved in noise-induced hearing loss.