Improvement in auditory function following pentazocine suggests a role for dynorphins in auditory sensitivity

The pharmacologic specificity of potentially beneficial drug effects on the auditory system were investigated. Changes in auditory sensitivity were evaluated in chinchillas following the infusion of an opioid narcotic. This drug (pentazocine) mimics endogenous opioid peptides (dynorphins), postulated to be chemical neurotransmitters (or neuromodulators) within the mammalian cochlea. In this study, two pentazocine enantiomers were investigated over a range of stimulus intensities. Significant baseline-relative changes in compound action potential (CAP) amplitudes were observed following intravenous administration of the kappa-opioid agonist (-)pentazocine (8 mg/kg). The sigma-receptor drug agonist (+)pentazocine (8 mg/kg) produced no measurable auditory effects. The magnitude of the (-)pentazocine effects were inversely related to stimulus intensity, up to 10 dB above threshold (i.e., 10 dB SL). Consistent with the observed amplitude doubling, auditory sensitivity was also improved an average 5-7 dB sound pressure level (SPL) following the administration of (-)pentazocine, while CAP response latencies and cochlear microphonic (CM) amplitudes remained unchanged. Results indicate stereospecific kappa-receptor mediated actions of pentazocine at the auditory nerve, and suggest an auditory role for neuroactive dynorphin peptides contained within the lateral efferent olivocochlear neurons.