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 (iv), this drug temporarily alters auditory nerve compound action potential (CAP) amplitudes. To test the hypothesis that the observed neural effects of iv (-)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. Design: In 31 normal-hearing, male pigmented chinchillas, amplitude changes in the click-evoked auditory CAP (N-1) were tracked at six stimulus intensities during a baseline and a postbaseline period in which iv (-)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 iv (-)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.