The effect of a GABAA agonist muscimol on acoustic injury of the mouse cochlea.
Gamma-aminobutyric acid (GABA) is one of major inhibitory neurotransmitter in the central nervous system and constitutes the cochlear efferent system. Glutamate excitotoxicity is implicated in the pathogenesis of acoustic injury of the cochlea. The present work investigated whether GABA(A) agonist muscimol can alleviate acoustic injury. Mice were exposed to a 4 kHz pure tone of 128 dB SPL for 4h. Muscimol and/or bicuculline, a GABA(A) antagonist, were intraperitoneally administered immediately before the onset of acoustic overexposure. The threshold shifts of the auditory brainstem response (ABR) and cochlear morphology after acoustic overexposure were then evaluated. Muscimol significantly decreased the ABR threshold shift and inhibited swelling of the afferent dendrites induced by acoustic overexposure. In addition, bicuculline inhibited the effects of muscimol. These findings suggest that activation of GABA(A) receptors reduces acoustic injury of the cochlea.
Murashita
Hidekazu
H
Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, Majors of Functional and Regulatory Medical Sciences, University of Tsukuba, Tsukuba, Japan.
Tabuchi
Keiji
K
Sakai
Shuhei
S
Uemaetomari
Isao
I
Tsuji
Shigeki
S
Hara
Akira
A
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D018755:GABA Agonists / Q000627:therapeutic use*; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D006198:Hair Cells, Auditory / Q000187:drug effects* / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000517:prevention & control; D051379:Mice; D009118:Muscimol / Q000627:therapeutic use*; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology; D009622:Noise / Q000009:adverse effects*; D011963:Receptors, GABA-A / Q000187:drug effects
D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D011963:Receptors, GABA-A; D009118:Muscimol; D001640:Bicuculline