The effects of acute stress-induced sleep disturbance on acoustic trauma-induced tinnitus in rats

Abstract

Chronic tinnitus is a debilitating condition and often accompanied by anxiety, depression, and sleep disturbance. It has been suggested that sleep disturbance, such as insomnia, may be a risk factor/predictor for tinnitus-related distress and the two conditions may share common neurobiological mechanisms. This study investigated whether acute stress-induced sleep disturbance could increase the susceptibility to acoustic trauma-induced tinnitus in rats. The animals were exposed to unilateral acoustic trauma 24 h before sleep disturbance being induced using the cage exchange method. Tinnitus perception was assessed behaviourally using a conditioned lick suppression paradigm 3 weeks after the acoustic trauma. Changes in the orexin system in the hypothalamus, which plays an important role in maintaining long-lasting arousal, were also examined using immunohistochemistry. Cage exchange resulted in a significant reduction in the number of sleep episodes and acoustic trauma-induced tinnitus with acoustic features similar to a 32 kHz tone at 100 dB. However, sleep disturbance did not exacerbate the perception of tinnitus in rats. Neither tinnitus alone nor tinnitus plus sleep disturbance altered the number of orexin-expressing neurons. The results suggest that acute sleep disturbance does not cause long-term changes in the number of orexin neurons and does not change the perception of tinnitus induced by acoustic trauma in rats.

Figure 1

ABR thresholds at different stimulus frequencies in the ipsilateral ear of the animals from the exposed-clean and exposed-dirty cage groups measured pre- and postexposure to acoustic trauma. Symbols represent means ± 1 SEM.

Figure 2

Sleep patterns during the 5.5 h cage exchange period. (a) Total number of sleep episodes during the 5.5 h period. (b) Number of sleep episodes during each hourly period. (c) Total duration of sleep during the 5.5 h period. (d) Average sleep duration for each sleep episode during each hourly period. (e) Time taken to fall asleep. (f) Sleep duration during each hourly period. Bars represent means ± 1 SEM.

Figure 3

Frequency discrimination curves for suppression ratio in sham, exposed-clean, and exposed-dirty animals in response to BBN, 20 kHz or 32 kHz stimuli at different intensities. Symbols represent means ± 1 SEM.

Figure 4

Orexin immunoreactivity in the hypothalamus. (a) A photograph showing orexin immunostaining located in the hypothalamus under a low magnification (scale bar: 1000 µm). Inserted picture showing the presence of orexin-positive staining in the cytoplasm and the processes of the neurons (scale bar: 100 µm). (b) Estimated total number of orexin-positive neurons in the ipsilateral and contralateral hypothalamus in sham, exposed-clean, and exposed-dirty animals. Bars represent means ± 1 SEM.