Synapse. 2020;74:e22128. wileyonlinelibrary.com/journal/syn | 1 of 11 https://doi.org/10.1002/syn.22128 © 2019 Wiley Periodicals, Inc 1 | INTRODUCTION The 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 com‐ plex 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, Received: 3 June 2019 | Revised: 7 August 2019 | Accepted: 8 August 2019 DOI: 10.1002/syn.22128 RESEARCH ARTICLE Opioid modulation of cochlear auditory responses in the rat inner ear Teresa Ramírez | Enrique Soto | Rosario Vega Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico Correspondence Rosario Vega, Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Apartado Postal 405, Puebla, Pue. CP 72000, Mexico. Email: rosario.vega@correo.buap.mx, axolotl_56@yahoo.com.mx Funding information Consejo Nacional de Ciencia y Tecnología (CONACyT), Grant/Award Number: Fronteras de la Ciencia 1544 Abstract The auditory system has an extensive efferent innervation, which contributes to pro‐ cesses 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, multi‐ ple 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 poten‐ tials (ABR), the compound action potential (CAP), and distortion products otacous‐ tic 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 ago‐ nists 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 af‐ ferent 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. KEYWORDS auditory loss, drug abuse, fentanyl, morphine, tramadol