Opioid modulation of cochlear auditory responses in the rat inner ear

Abstract

| INTRODUC TI ONThe primary neurotransmitter released by the efferent terminals of the olivocochlear pathway is acetylcholine (ACh), which binds to nicotinic ACh α9-α10 located at the base of the outer hair cell (OHC) (Taranda et al., 2009), and M2 and M4 muscarinic receptors, in the synaptic complex of both the lateral olivocochlear pathway (LOC) and the medial olivocochlear pathway (MOC) (Maison et al., 2010). ACh and the calcitonin gene-related peptide co-localize in the efferent neurons of the OC bundle. Immunoreactivity to γ-aminobutyric acid was also detected in the OC cochlear efferents, although it seems to be limited to the apex of the cochlea (Maison, Adams, & Liberman, 2003; Maison, Casanova, AbstractThe auditory system has an extensive efferent innervation, which contributes to processes of control and regulation of the afferent input. The expression of receptors to various neurotransmitters and neuropeptides in the inner ear has been described, among which endogenous opioid receptors are found. The role of opioid receptors in the cochlea is not yet fully defined, it has been reported that opioid agonists and antagonists modulate the response to auditory stimuli and in clinical practice, multiple cases have been reported in which the consumption of opioid derivatives induce sensorineural hearing loss. In this work, we evaluated the effects of acute treatment with morphine, fentanyl, tramadol, and naloxone, in the auditory brain stem potentials (ABR), the compound action potential (CAP), and distortion products otacoustic emissions (DPOAE), across a wide range of stimulus frequencies and amplitudes.Adult Long-Evans rats of the strain CII/ZV weighing 180-220 g were used. For the ABR recording drugs were administered intraperitoneally or intravenously. For the CAP and DPOAE drugs were applied by direct perfusion in the middle ear. The opioid agonists produced a consistent increase in the amplitude of the PI component of the ABR and of the N1-P1 amplitude of the CAP. Naloxone produced no significant changes in the ABR and a reduction of the CAP N1-P1 amplitude. Also, opioid agonists induced a decrease in the amplitude of the DPOAE. These results show that the opioid receptor activation modulates both the afferent response at both the afferent response to acoustic stimuli, and also at the cochlear mechanics as revealed by DPOAE changes. These results present a significant step in understanding how opioid modulation of auditory responses may contribute to the auditory processing and to sensorineural hearing loss produced by opioids. K E Y W O R D Sauditory loss, drug abuse, fentanyl, morphine, tramadol

Auditory brainstem responses are resistant to pharmacological modulation in Sprague Dawley wildtype and Neurexin1α knockout rats

“…Our findings are in line with previous studies, showing a lack of ABRs and hearing threshold modulation with retigabine 65 . Beyond our own findings with other compounds (such as benzodiazepine, baclofen or bitopertin), the notion of a more general issue with pharmacological modulation of ABRs, is further supported by other rodent studies, demonstrating the lack ABRs modulation with opioids 66 . This is different to earlier studies demonstrating that theophylline 67 or cocaine 68 change ABRs characteristics likely due to ototoxic rather than neuromodulatory effects.…”

Opioid receptor activation modulates the calcium current in the cochlear outer hair cells of the rat

“…The activation of κ opioid receptors increased the N1 and N2 components of the auditory brain stem potentials (ABR) (Sahley et al, 1991). The opioid agonists (morphine, fentanyl, and tramadol) decreased the amplitude of distortion product otoacoustic emissions (Ramírez et al, 2020).…”

Sensorimotor Alterations Induced by Novel Fentanyl Analogs in Mice: Possible Impact on Human Driving Performances

“…The temporary loss of hearing produced by methadone has also been reported [ 80 , 81 ]. The fact that opioid receptors, in particular, mu ones are expressed in the inner ear of mice confirms their involvement in the acoustic alterations produced in mice after acute systemic administration of FENS and that could be related to temporary dysfunction of the cochlea, which was prevented by NLX pre-treatment in our test [ 82 ].…”