Effects of pentylenetetrazole and 4-aminopyridine on the auditory brainstem response (ABR) and on the hearing sensitivity in the guinea pig in vivo.

For exploring a possible connection between the reduced hearing sensitivity and certain abnormalities in the auditory brainstem responses (ABRs) in generalized epilepsy, the effects of two convulsing agents, namely pentylenetetrazole (PTZ) and of 4-aminopyridine (4-AP), on: (1). the cortical activity (EEG), (2). the hearing threshold and (3). the amplitudes and latencies of the ABR waves evoked by a stimulus of high intensity (100 dB) were investigated in guinea pigs. All animals injected (i.p.) with 100mg/kg PTZ or with 2mg/kg 4-AP developed generalized seizures, followed by characteristic EEG patterns for the post-ictal period, that were accompanied by a marked reduction of the hearing sensitivity (as indicated by the elevated threshold of the ABR), as well as by retro-cochlear changes (as judged by the changes in the later ABR waves in response to 100 dB). For instance, both convulsing agents decreased the amplitude and increased the latency of P4, that is the wave component of the ABRs generated in the lateral superior olivary nucleus and while PTZ increased the latency of P3, the wave component of the ABRs generated in the medial superior olivary nucleus, 4-AP dramatically increased its amplitude. Comparison of recordings taken at specific times for the duration of the post-ictal period (i.e. within about 1h for PTZ and 2h for 4-AP) reveals that the extent of the changes on the EEG matches with the increase in the auditory threshold and with the extent of the changes on the later waves of the ABR elicited by 100 dB. These data indicate that changes in the activity of the lateral and the medial nuclei of the superior olivary complex (SOC) accompany the hearing loss and the post-ictal epileptic cortical activity.