Effects of opioid be drugs on auditory evoked potentials suggest a role of lateral olivocochlear dynorphins in auditory function.
Multiple gene products of opioid peptide families (e.g., enkephalins, dynorphins) with differing opioid receptor specificities are present within olivocochlear efferent terminals. Enkephalins activate mu- and delta-opioid receptors, and are generally inhibitory in the nervous system, and dynorphins are kappa-receptor agonists, which may be excitatory to postsynaptic neurons. We have examined the effects of intravenously administered opioid agonists and antagonists on click-evoked N1 and N2 amplitudes and latencies of the compound action potential in the chinchilla recorded at the round window. Parenteral administration of the opioid receptor antagonist naloxone or the potent mu-receptor agonist fentanyl did not alter N1 and N2 amplitudes or latencies. The kappa-receptor agonist, mu-receptor antagonist pentazocine caused marked increases in N1 and N2 amplitudes over baseline values at threshold intensities. These effects were not abolished by naloxone. No effects were seen on the cochlear microphonic, supporting a site of action of these effects at the lateral olivocochlear efferent terminals on auditory nerve dendrites under inner hair cells. Similar results were obtained when far field auditory evoked responses were recorded. Results were obtained under ketamine/pentobarbital anesthesia, which provided stable recording baselines in contrast to tiletamine/zolezepam/pentobarbital, with which an upward drift in auditory potentials was observed. This stimulatory action of kappa-agonists on auditory-evoked potential amplitudes appears to represent a physiological role of the lateral olivocochlear efferent innervation. The different neurotransmitters of the olivocochlear efferents (e.g. enkephalins, dynorphins, acetylcholine) may have antagonistic actions on auditory potentials, as may the lateral and medial systems themselves.
Department of Psychiatry, Dartmouth Medical School, Hanover, New Hampshire 03756.
T L
TL
Sahley
R B
RB
Kalish
F E
FE
Musiek
D W
DW
Hoffman
D000818:Animals; D001309:Auditory Threshold / Q000502:physiology; D002682:Chinchilla; D003051:Cochlea / Q000502:physiology; D004399:Dynorphins / Q000502:physiology; D004525:Efferent Pathways / Q000502:physiology; D004723:Endorphins / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000502:physiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D009847:Olivary Nucleus / Q000502:physiology; D011957:Receptors, Opioid / Q000502:physiology
D004723:Endorphins; D011957:Receptors, Opioid; D004399:Dynorphins