Comparison of Salicylate- and Quinine-Induced Tinnitus in Rats

Abstract

Background-Salicylate and quinine have been shown to reliably induce short-term tinnitus when administered at high doses. The present study compared salicylate and quinine induced tinnitus in rats using the gap prepulse inhibition of acoustic startle (GPIAS).Methods-Twenty-four rats were divided into 2 groups; the first group (n=12) was injected with salicylate (300 mg/kg/d), the second (n=12) was treated with quinine orally at a dose of 200 mg/kg/ d. Animals were treated daily for 4 consecutive days. All rats were tested for tinnitus and hearing loss before and 2, 24, 48, 72, 96 hours after the first drug administration. Tinnitus was assessed using GPIAS; hearing function was measured with DPOAEs and ABR.Results-Salicylate treatment induced transient tinnitus with a pitch near 16 kHz starting 2 h posttreatment, persisting over the 4-day treatment period and disappearing 24 h later. Animals in the quinine group showed GPIAS changes at a higher pitch (20 kHz); however, changes were more variable among animals and the mean data were not statistically significant. Hearing function varied across treatments. In the salicylate group, high-level DPOAEs were slightly affected; most changes occurred 2 h post-treatment. Low-level DPOAEs were affected at all frequencies with a progressive dose-dependent effect. In the quinine group, only high-level DPOAEs were affected, mainly at 16 kHz.Conclusion-The present study highlights the similarities and differences in the frequency and the time course of tinnitus and hypoacusis induced by salicylate and quinine. Transient tinnitus was reliably induced pharmacologically with salicylate while hearing loss remained subclinical with only minor changes in DPOAEs.

Time course of tinnitus development following noise exposure in mice

“…These results are consistent with previous studies showing that rats with behavioral evidence of tinnitus from either the lever-pressing approach of Brozoski & Bauer (2006), or the polydypsia approach of Lobarinas and Salvi (Yang, 2007) demonstrated a degraded ability to process silent cues using the same GPIAS procedures employed here. Additional recent studies have also demonstrated the use of GPIAS methods for measuring tinnitus to address a variety of experimental questions [e.g., Wang, et al, 2009; Ralli, et al, 2010; Zhang, et al, 2010]. The current study also demonstrates a time of apparent hyperacusis in behavioral responses to prepulse stimuli (Figure 6) for a period of 2–3 weeks following noise exposure, consistent with a hyperexcitable auditory system.…”

Salicylate-induced cochlear impairments, cortical hyperactivity and re-tuning, and tinnitus

“…Robust DPOAEs were present at all 6 test frequencies (F 2 =6, 8, 12, 16, 24, and 30 kHz respectively) before SS treatment. However, at 2 h post-treatment, DPOAE amplitudes had decreased significantly at low frequencies (2F 1 -F 2 ≤ 10.7 kHz) and high frequencies (2F 1 -F 2 ≥ 20 kHz), whereas little change occurred at the mid-frequencies (2F 1 -F 2 =16 kHz), a frequency region previously associated with the pitch of salicylate-induced tinnitus (Ralli et al, 2010; Yang et al, 2007). The mild reduction in mid-frequency DPOAEs surrounded by large losses at low and high frequencies could alter the tonotopic organization in the CNS as discussed below.…”

A novel behavioural approach to detecting tinnitus in the guinea pig

“…Salicylate causes transient and reversible tinnitus when administered at high doses in both humans (Mongan et al, 1973) and animals (Ralli et al, 2010). Behaviourally, salicylate has been shown to significantly impair gap detection in rats (Turner and Parrish, 2008), consistent with the results shown here.…”

“…The development of animal models of tinnitus has played an essential role in furthering our knowledge of the physiological and molecular mechanisms that underlie this condition (Kaltenbach, 2011). The most common trigger for the condition is repeated exposure to excessive loud noise (Eggermont and Roberts, 2004), but among others it can also occur as a result of the effects of ototoxic drugs such as sodium salicylate or quinine (Ralli et al, 2010). Sodium salicylate is frequently the cause of tinnitus when patients receive high doses of aspirin (Cazals, 2000).…”