Naloxone blockade of (-)pentazocine-induced changes in auditory function.
OBJECTIVE
In a previous report, we found that intravenous (i.v.) (-)pentazocine improved auditory sensitivity and significantly altered compound action potential (CAP) amplitudes. Its sigma (sigma)-receptor-selective optical isomer (+)pentazocine administered at the same dose was without effect, suggesting that the observed auditory neural effects might be mediated by an opioid receptor. To directly test this hypothesis, in the present investigation we attempted to antagonize the auditory neural effects of (-)pentazocine using the pure, nonspecific drug antagonist naloxone.


METHODS
In 25 normal-hearing, male, pigmented chinchillas, amplitude and latency changes in the click-evoked auditory nerve CAP (N1) and cochlear microphonic (CM) were tracked at six stimulus intensities during a baseline period and after the postbaseline administration of the opioid drug agonist (-)pentazocine (16 mg/kg; i.v.). In separate groups of chinchillas, (-)pentazocine was given alone or administered in combination with the standard opioid receptor antagonist naloxone administered at two doses.


RESULTS
Robust changes in CAP amplitudes after (-)pentazocine occurred in the absence of measurable alterations in CAP response latencies, CM amplitudes, or blood chemistries and were significantly antagonized when naloxone (5 mg/kg) was added to the i.v. infusion.


CONCLUSIONS
The observed blockade clearly indicates that the agonist effects of (-)pentazocine are opioid receptor-mediated and suggests a connection between opioid receptors and auditory neural function. Mechanisms of action and the connection between an opioid modulation of auditory function and stress, hyperacusis, and tinnitus are discussed.
Sahley
T L
TL
Department of Speech & Hearing, Cleveland State University, Ohio, USA.
Musiek
F E
FE
Nodar
R H
RH
D000818:Animals; D001307:Auditory Perception / Q000187:drug effects*; D001774:Blood Chemical Analysis; D002682:Chinchilla; D003051:Cochlea / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010423:Pentazocine / Q000009:adverse effects* / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; D010423:Pentazocine