Evaluation of brain SERT with 4-[ 18 F]-ADAM/micro-PET and hearing protective effects of dextromethorphan in hearing loss rat model

Toxicol Appl Pharmacol. 2019 Sep 1;378:114604. doi: 10.1016/j.taap.2019.114604. Epub 2019 May 30.

Abstract

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-4-18F-fluorophenylthio)benzylamine (4-[18F]-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.

Keywords: 4-[(18)F]-ADAM; Dextromethorphan; Micro-PET; Noise-Induced Hearing Loss; SERT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzylamines / pharmacology*
  • Brain / drug effects*
  • Brain / metabolism
  • Brain Stem / drug effects
  • Brain Stem / metabolism
  • Dextromethorphan / pharmacology*
  • Disease Models, Animal
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Hearing Loss / drug therapy*
  • Hearing Loss / metabolism*
  • Male
  • N-Methylaspartate / pharmacology
  • Positron-Emission Tomography / methods
  • RNA-Binding Proteins / metabolism*
  • Radiopharmaceuticals / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonergic Neurons / drug effects
  • Serotonergic Neurons / metabolism
  • Serotonin Plasma Membrane Transport Proteins / metabolism

Substances

  • Benzylamines
  • RNA-Binding Proteins
  • Radiopharmaceuticals
  • Serotonin Plasma Membrane Transport Proteins
  • Sert1 protein, rat
  • N-Methylaspartate
  • Dextromethorphan
  • benzylamine