Temporal Effects of Acoustic Trauma-Induced Tinnitus on the Extracellular Levels of Amino Acids in the Inferior Colliculus of Rats.

Abstract

Tinnitus is often defined as the perception of sound in the absence of a physical or an external acoustic source. While the exact underlying causes of tinnitus remain poorly understood, there is growing evidence to suggest that tinnitus is caused by neuronal hyperactivity at different levels of the central auditory pathways, including the inferior colliculus. The functions of neurons depend on their underlying neurochemistry. Therefore, an increase in the activity of neurons following acoustic trauma-induced tinnitus could be reflected in regional alterations of the neurochemical profile within the central auditory system. The aim of this study was to investigate the effects of acoustic trauma-induced tinnitus on the basal concentration of extracellular amino acids in the inferior colliculus of rats, at 1-week and 2-month following intense noise exposure. In addition to this, changes in extracellular amino acid concentrations within the rat inferior colliculus in response to different sound stimulations, at 1-week and 2- month following acoustic trauma, were also examined. Tinnitus was induced by exposure to acoustic trauma (a 16 kHz, 115 dB pure tone presented unilaterally for 1 h), and the presence of tinnitus in animals from the 2-month group was assessed using a conditioned lick- suppression paradigm. Using in vivo microdialysis and high-performance liquid chromatography, the extracellular concentration of 7 amino acids in the inferior colliculus of rats, at 1-week and 2-month following acoustic trauma, were measured. Hearing loss in the noise-exposed ear was evident immediately after the acoustic trauma, as indicated by a significant increase in the auditory brainstem-evoked response threshold in exposed animals from the 1-week (P ≤ 0.004), and 2-month (P ≤ 0.002) groups. At 2-month after acoustic trauma, 7 out of 13 exposed animals exhibited behavioural signs of tinnitus when tested using a conditioned lick-suppression paradigm. No statistically significant differences were found when comparing the basal amino acid concentrations between the sham and exposed animals from the 1-week survival group (P ≥ 0.05). Similarly, no significant differences in the basal concentrations of amino acids between the exposed-tinnitus, exposed-no tinnitus and sham animals were found at 2-month after intense noise exposure. However, when amino acid levels in response to different sound stimulations were investigated, exposure had a significant effect on the concentration of glutamate, which varied with respect to frequency, and as a function of the sound stimulation on/off periods in the 1-week group (P ≤ 0.028). Glutamate concentration in the exposed animals was higher compared to the sham controls in response to 4 kHz, 8 kHz and 16 kHz tones irrespective of the animals developed tinnitus or not. This result suggests that more neurons may be activated in the exposed animals in response to sound stimuli, which may contribute to the increased neuronal activity associated with intense noise exposure. A significant sound stimulation on/off effect on the concentration of taurine was also observed in the 1-week (P ≤ 0.0001), and 2-month (P ≤ 0.0001) groups. This implies that taurine may be actively involved in shaping the response properties of neurons in response to sound stimuli. In addition, there was a significant sound stimulation on/off effect (P ≤ 0.05) and a frequency effect (P ≤ 0.033) for threonine, as indicated by a decrease in threonine levels in response to sound stimuli, irrespective of whether the animals were exposed to acoustic trauma or not. This could be related to the general depression of amino acid metabolism in response to sound stimuli. These results suggest that although the extracellular concentration of amino acids remains unchanged at rest condition, they may contribute to an altered neuronal response to sound stimuli following acoustic trauma.