Blockade of opioid-induced changes in auditory function at the level of the cochlea.
OBJECTIVE
We have previously investigated the auditory neural effects of the kappa-opioid receptor agonist, (-)pentazocine. When administered intravenously (i.v.), this drug temporarily alters auditory nerve compound action potential (CAP) amplitudes. To test the hypothesis that the observed neural effects of i.v. (-)pentazocine occur via kappa-receptor interactions within the cochlea, we attempted to block these effects by employing a specific kappa-opioid receptor antagonist applied directly to the cochlear round window (RW) membrane.


METHODS
In 31 normal-hearing, male pigmented chinchillas, amplitude changes in the click-evoked auditory CAP (N1) were tracked at six stimulus intensities during a baseline and a postbaseline period in which i.v. (-)pentazocine (8 mg/kg) was administered. (-)Pentazocine administration was preceded by the delivery to the cochlear RW membrane of an artificial perilymph solution given alone or containing the kappa-opioid receptor selective antagonist, norbinaltorphimine (Nor-BNI), which was administered at two concentrations in separate groups of animals.


RESULTS
The amplitude increase in the CAP after (-)pentazocine was significantly reduced when i.v. (-)pentazocine was preceded by RW-administered Nor-BNI (4 mM).


CONCLUSIONS
The reversibility of agonist effects by Nor-BNI indicates direct or indirect opioid kappa-receptor-mediated auditory neural effects at the level of the cochlea and suggests a connection between kappa-receptors and auditory neural function.
Sahley
T L
TL
Department of Speech & Hearing and Biology, Cleveland State University, Ohio, USA.
Nodar
R H
RH
Musiek
F E
FE
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002682:Chinchilla; D003051:Cochlea / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010423:Pentazocine / Q000008:administration & dosage / Q000494:pharmacology*; D012405:Round Window, Ear / Q000187:drug effects; D000159:Vestibulocochlear Nerve / Q000187:drug effects
D009292:Narcotic Antagonists; D010423:Pentazocine