Rapid, reversible elimination of medial olivocochlear efferent function following single injections of gentamicin in the guinea pig.
Measurements were made of the ability of nonsimultaneous, contralaterally presented broadband noise maskers to suppress ipsilaterally-evoked compound action potentials (CAPs) of the auditory nerve to 8-kHz tone pips in guinea pigs. Contralateral acoustic stimuli have been shown to suppress responses to ipsilateral stimuli through the action of the medial olivocochlear efferent bundle. In this study, maximum suppression across subjects ranged from 2-6 dB. The ability of the contralateral noise to suppress ipsilateral CAPs was rapidly reduced beginning within minutes of a single intramuscular injection of the aminoglycoside antibiotic gentamicin (150 mg/kg), and, in general, was completely abolished by 1.5-2 h. Changes in suppression were presumably produced by gentamicin-induced blockade of presynaptic calcium channels on the medial olivocochlear efferents and closely follow the pharmacokinetics of gentamicin in perilymph. Reductions in efferent-mediated suppression were observed in the absence of any measurable change in either CAP thresholds to different frequencies or CAP input/output. Suppression was partially restored in some animals after 24 h, and was fully recovered in all subjects within 96 h postinjection. The present studies suggest that measures of efferent function might form the rational basis for an objective means to assess aminoglycoside insult on the cochlea in the absence of hair cell damage. These results also indicate that single injections of gentamicin offer a reversible, non-invasive model in which medial efferent function can be studied in behavioral animals.
Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, NC 27710.
D W
DW
Smith
J P
JP
Erre
J M
JM
Aran
D000161:Acoustic Stimulation; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D004558:Electric Stimulation; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D009476:Neurons, Efferent / Q000187:drug effects* / Q000502:physiology; D000159:Vestibulocochlear Nerve / Q000502:physiology
D002121:Calcium Channel Blockers; D005839:Gentamicins