Bi-phasic intensity-dependent opioid-mediated neural amplitude changes in the chinchilla cochlea: Partial blockade by an N-Methyl-d-Aspartate (NMDA)-receptor antagonist
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- 作者：Tony L. Sahley ; David J. Anderson ; Cheryl L. Chernicky
- 关键词：(+)-MK-801 (dizocilpine hydrogen maleate) ; U-50488H ; (− ; )-pentazocine ; N-Methyl-d-Aspartate (NMDA) receptors ; Lateral efferent olivocochlear system ; κ ; -Opioid receptors ; Dynorphins ; Glutamate ; Auditory nerve
- 刊名：European Journal of Pharmacology
- 出版年：2008
- 出版时间：2 February 2008
- 年：2008
- 卷：580
- 期：1-2
- 页码：100-115
- 全文大小：847 K
文摘
Dynorphins, glutamate, and glutamate-sensitive N-Methyl-d-Aspartate (NMDA) receptors exist in the mammalian cochlea. Dynorphins produce neural excitation and excitotoxic effects in the spinal cord through a κ-opioid facilitation of NMDA receptor-sensitivity to glutamate. The κ-opioid receptor drug agonists N-dimethylallyl-normetazocine [(−)-pentazocine (50 mmol)] and trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide [U-50488H (100 mmol)] were administered across the cochlear round window membrane in the chinchilla. Each drug produced significant post-baseline amplitude changes in the click-evoked auditory nerve compound action potential. Amplitude changes at threshold amounted to increases in sensitivity that ranged from 4–8 decibels, measured in sound pressure level (dB SPL). The large neural amplitude increases at threshold were accompanied by progressively smaller amplitude changes at 5 and 10 dB above threshold (dB SL). However, at stimulus intensities ≥ 20 dB SL, post-baseline neural amplitudes were suppressed to levels below baseline and control values. These bi-phasic intensity-dependent neural amplitude changes have never before been observed following i.v. administered (−)-pentazocine in this species. Finally, the bi-phasic neural amplitude changes in U-50488H-treated (100 mmol) animals were partially blocked (except at 20 dB SL), following a round window pre-treatment with the NMDA receptor drug antagonist, dizocilpine hydrogen maleate [(+)-MK-801 (8 mmol)]. Our data suggests that endogenous dynorphins within lateral efferent olivocochlear neurons differentially modulate auditory neural excitation, possibly through cochlear NMDA receptors and glutamate. The role played by lateral efferent opioid neuromodulation at cochlear NMDA receptors, is discussed.