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

Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study

“…In the present study, we demonstrated that DXM, widely used and available in numerous over-the-counter cough and cold preparations worldwide [ 16 ], also has a protective effect against NIHL. The result was compatible to our previous report in a NIHL rat model using 4-[ 18 F]-ADAM/micro-PET and showed DXM prevent hearing loss and preserved brain serotonin transporter function [ 21 ]. This effect also has been proven previously that DXM moderately ameliorated the compound action potential threshold shift in cochlear dysfunction induced by transient ischemia [ 17 ].…”

“…In 2010, the U.S. Food & Drug Administration approved the use of DXM in combination with quinidine for the treatment of pseudobulbar affect characterized by sudden and involuntary episodes of crying, laughing, or other emotional displays secondary to a neurological disease or brain injury, such as amyotrophic lateral sclerosis, stroke, Alzheimer’s disease, multiple sclerosis, Parkinson’s disease, and TBI [ 16 ]. To date, except our previous published paper, there is sparse study to explore the association between DXM use and preventing SNHL in inner ear of mouse model and human study [ 21 ]. Herein, we explore whether DXM, an NMDA antagonist, exhibits any potential effect against SNHL in both animal models and population-based study.…”

Resveratrol prevents hearing loss and a subregion specific- reduction of serotonin reuptake transporter induced by noise exposure in the central auditory system

“…Our present study mainly focused the impact of noise exposure on SERT expression in the central auditory system, thus we did not detect morphological changes in the cochlea of the peripheral auditory system of mice. Previous studies have reported that noise trauma not only induce hearing loss, but also down-regulate the SERT expression in the central auditory system, including IC and Au1 (Li et al, 2019;Liu et al, 2019). Several studies used Small-Animal Positron Emission Tomography (PET) with N, N-dimethyl -ADAM, a specific radioactive ligand for SERT) to evaluate SERT changes in the control and noise exposure conditions, and suggest that noise exposure decreases markedly SERT expression in the central auditory system (Kang et al, 2013;Li et al, 2019).…”

“…A previous study has shown that chronic broadband white noise exposure can increase extracellular 5-HT concentrations in the rat cerebellum, hypothalamus, pons, and striatum (Ravindran et al, 2005). Some studies also showed that noise exposure can cause the loss of the serotonin reuptake transporter (SERT) in the IC, frontal cortex, hippocampus, striatum, thalamus, hypothalamus, midbrain, and auditory cortex (Kang et al, 2013;Liu et al, 2019). In addition, noise exposure can induce an increase in 5-HT level in the central auditory system (Cransac et al, 1998), and the increase of 5-HT level in the central auditory system may be related to the generation of tinnitus (Simpson and Davies, 2000;Liu et al, 2003), a condition associated with neuronal hyperactivity in the central auditory system (Kaltenbach and Godfrey, 2008;Olthof et al, 2022).…”