title: Chronic excitotoxicity in the guinea pig cochlea induces temporary functional deficits without disrupting otoacoustic emissions.
abstract: Brief cochlear excitotoxicity produces temporary neural swelling and transient deficits in auditory sensitivity; however, the consequences of long-lasting excitotoxic insult have not been tested. Chronic intra-cochlear infusion of the glutamate agonist AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) resulted in functional deficits in the sound-evoked auditory brainstem response, as well as in behavioral measures of hearing. The electrophysiological deficits were similar to those observed following acute infusion of AMPA into the cochlea; however, the concentration-response curve was significantly shifted as a consequence of the slower infusion rate used with chronic cochlear administration. As observed following acute excitotoxic insult, complete functional recovery was evident within 7 days of discontinuing the AMPA infusion. Distortion product otoacoustic emissions were not affected by chronic AMPA infusion, suggesting that trauma to outer hair cells did not contribute to AMPA-induced deficits in acoustic sensitivity. Results from the current experiment address the permanence of deficits induced by chronic (14 day) excitotoxic insult as well as deficits in psychophysical detection of longer duration acoustic signals.
authors.affiliation: Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0506, USA. colleeng@umich.edu
authors.forename: Colleen G
authors.initials: CG
authors.lastname: Le Prell
authors.forename: Masao
authors.initials: M
authors.lastname: Yagi
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Beyer
authors.forename: Graham
authors.initials: G
authors.lastname: Atkin
authors.forename: Yehoash
authors.initials: Y
authors.lastname: Raphael
authors.forename: David F
authors.initials: DF
authors.lastname: Dolan
authors.forename: Sanford C
authors.initials: SC
authors.lastname: Bledsoe
authors.forename: David B
authors.initials: DB
authors.lastname: Moody
mesh_terms: D000818:Animals; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D003056:Cochlear Nerve / Q000187:drug effects*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D008297:Male; D009355:Neomycin / Q000494:pharmacology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology / Q000633:toxicity*
chemical_list: D018690:Excitatory Amino Acid Agonists; D011500:Protein Synthesis Inhibitors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D009355:Neomycin