Evaluation of brain SERT with 4-[F]-ADAM/micro-PET and hearing protective effects of dextromethorphan in hearing loss rat model.

Toxicol Appl Pharmacol

Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan; Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan; School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Electronic address:

Published: September 2019

This study investigated the protective effects of dextromethorphan (DXM) on noise-induced hearing loss (NIHL) in rats. This study aimed to improve the auditory threshold and to understand the protective effects of DXM against N-methyl-d-aspartate (NMDA)-induced neurite degeneration of serotonergic neurons. The animals were exposed to 8-kHz narrowband noise at a 118-dB sound pressure level for 3.5 h. The hearing thresholds were determined by measuring the auditory brainstem response to click stimuli. Serotonin transporter (SERT) expression was determined through micro-positron emission tomography (PET) using N,N-dimethyl-2-(2-amino-4-F-fluorophenylthio)benzylamine (4-[F]-ADAM). We also investigated the effects of DXM on NMDA-induced morphological changes in the primary cultures of rat serotonergic neurons. NIHL significantly improved after prophylactic treatment with DXM (p < .05). SERT density in DXM-treated rats was significantly higher than that in non-DXM-treated rats. Because prophylactic medication restored the NMDA-inhibited neurite length of serotonergic neurons and presented SERT density, DXM could be a potential agent in alleviating NIHL.

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http://dx.doi.org/10.1016/j.taap.2019.114604DOI Listing

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