Abstract
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Objectives Serotonin transporter (SERT) is an integral membrane protein which located on pre-synaptic serotonergic neurons. Our previous studies have demonstrated that noise-induced hearing loss involves a reduction in SERT expression in various regions of the rat brain using small animal-PET. In this study, we used 4-[18F]-ADAM (a serotonin transporter imaging agent) and small animal-PET to study in vivo the effects of citalopram (a selective serotonin reuptake inhibitor) on noise-induced loss of SERT in rat brain.
Methods The male Sprague Dawley rats were deafened in both ears by noise overexposure (116 dB sound pressure level, 8 kHz narrowband noise, for 3.5 h under general anesthesia) for 4 consecutive days. Rats were treated with citalopram (20 mg/kg, i.p.) on the third day. An auditory brainstem response test and 4-[18F]-ADAM/small animal PET were performed at different time points (1 day, 1 week, and 4weeks) after noise exposure. Specific 4-[18F]-ADAM uptake ratios (SURs) were calculated from the PET imaging data for various brain regions. The SURs were expressed as (target regioncerebellum)/cerebellum. Immunohistochemistry was performed 1 days after the last PET scan.
Results The preliminary data show that noise-Induced hearing loss could cause the decrease of 4-[18F]-ADAM uptake in various brain regions, such as midbrain, thalamus, hypothalamus, striatum and frontal cortex on the fifth day (by approximately 27-40% compared to control values). When the noise-exposure rat treated with citalopram, the decrement of SUR is less than those of untreated (hear loss) group. The studies of serotonin transporter immunostaining were comparable to the PET imaging results in various brain regions.
Conclusions The results suggest that citalopram provides neuroprotection against noise-induced loss of SERT and that such neuroprotection is detectable in vivo by 4-[18F]-ADAM/small animal-PET.