Advertisement

Behavioral Animal Model of the Emotional Response to Tinnitus and Hearing Loss

  • Amanda M. LauerEmail author
  • Gail Larkin
  • Aikeen Jones
  • Bradford J. May
Research Article

Abstract

Increased prevalence of emotional distress is associated with tinnitus and hearing loss. The underlying mechanisms of the negative emotional response to tinnitus and hearing loss remain poorly understood, and it is challenging to disentangle the emotional consequences of hearing loss from those specific to tinnitus in listeners experiencing both. We addressed these questions in laboratory rats using three common rodent anxiety screening assays: elevated plus maze, open field test, and social interaction test. Open arm activity in the elevated plus maze decreased substantially after one trial in controls, indicating its limited utility for comparing pre- and post-treatment behavior. Open field exploration and social interaction behavior were consistent across multiple sessions in control animals. Individual sound-exposed and salicylate-treated rats showed a range of phenotypes in the open field, including reduced entries into the center in some subjects and reduced locomotion overall. In rats screened for tinnitus, less locomotion was associated with higher tinnitus scores. In salicylate-treated animals, locomotion was correlated with age. Sound-exposed and salicylate-treated rats also showed reduced social interaction. These results suggest that open field exploratory activity is a selective measure for identifying tinnitus distress in individual animals, whereas social interaction reflects the general effects of hearing loss. This animal model will facilitate future studies of the structural and functional changes in the brain pathways underlying emotional distress associated with hearing dysfunction, as well as development of novel interventions to ameliorate or prevent negative emotional responses.

Keywords

tinnitus distress anxiety depression hearing loss sound exposure salicylate 

Notes

Acknowledgments

Supported by grants from the Tinnitus Research Consortium, Action on Hearing Loss, National Institutes of Health grant DC005211, a gift from Liquing Zeng, and the David M. Rubenstein Fund for Hearing Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflicts of interest.

References

  1. Altun M, Bergman E, Edström E, Johnson H, Ulfhake B (2007) Behavioral impairments of the aging rat. Physiol Behav 92:911–923CrossRefPubMedGoogle Scholar
  2. Andersson G, Kaldo V (2004) Internet-based cognitive behavioral therapy for tinnitus. J Clin Psychol 60:171–178CrossRefPubMedGoogle Scholar
  3. Andersson G, Vretblad P (2000) Anxiety sensitivity in patients with chronic tinnitus. Scand J Behav Ther 29:57–64CrossRefGoogle Scholar
  4. Arlinger S (2003) Negative consequences of uncorrected hearing loss--a review. Int J Audiol 42 Suppl 2:2S17–2S20PubMedGoogle Scholar
  5. Asin KE, Wirtshafter D, Kent EW (1979) Straight alley acquisition and extinction and open field activity following discrete electrolytic lesions of the mesencephalic raphe nuclei. Behav Neural Biol 25:242–256CrossRefPubMedGoogle Scholar
  6. Bauer CA, Kurt W, Sybert LT, Brozoski TJ (2013) The cerebellum as a novel tinnitus generator. Hear Res 295:130–139CrossRefPubMedPubMedCentralGoogle Scholar
  7. Budd RJ, Pugh R (1995) The relationship between locus of control, tinnitus severity, and emotional distress in a group of tinnitus sufferers. J Psychosom Res 39:1015–1018CrossRefPubMedGoogle Scholar
  8. Caligiuri MP, Ellwanger J (2000) Motor and cognitive aspects of motor retardation in depression. J Affect Disord 57:83–93CrossRefPubMedGoogle Scholar
  9. Carobrez A, Bertoglio L (2005) Ethological and temporal analyses of anxiety-like behavior: the elevated plus-maze model 20 years on. Neurosci Biobehav Rev 29:1193–1205CrossRefPubMedGoogle Scholar
  10. Chen G, Stolzberg D, Lobarinas E, Sun W, Ding D, Salvi R (2013) Salicylate-induced cochlear impairments, cortical hyperactivity and re-tuning, and tinnitus. Hear Res 295:100–113CrossRefPubMedGoogle Scholar
  11. Chen Y, Li X, Liu L, Wang J, Lu C, Yang M, Jiao Y, Zang F, Radziwon K, Chen G (2015) Tinnitus and hyperacusis involve hyperactivity and enhanced connectivity in auditory-limbic-arousal-cerebellar network. elife 4:e06576PubMedPubMedCentralGoogle Scholar
  12. Cheng L, Wang S, Huang Y, Liao X (2016) The hippocampus may be more susceptible to environmental noise than the auditory cortex. Hear Res 333:93–97CrossRefPubMedGoogle Scholar
  13. Davis A, Rafaie EA (2000) Epidemiology of tinnitus. Tinnitus handbook:1–23Google Scholar
  14. Dawes P, Emsley R, Cruickshanks KJ, Moore DR, Fortnum H, Edmondson-Jones M, McCormack A, Munro KJ (2015) Hearing loss and cognition: the role of hearing AIDS, social isolation and depression. PLoS One 10:e0119616CrossRefPubMedPubMedCentralGoogle Scholar
  15. Deacon RM, Bannerman DM, Kirby BP, Croucher A, Rawlins JNP (2002a) Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery. Behav Brain Res 133:57–68CrossRefPubMedGoogle Scholar
  16. Deacon RM, Croucher A, Rawlins JNP (2002b) Hippocampal cytotoxic lesion effects on species-typical behaviours in mice. Behav Brain Res 132:203–213CrossRefPubMedGoogle Scholar
  17. Dineen R, Doyle J, Bench J (1997) Audiological and psychological characteristics of a group of tinnitus sufferers, prior to tinnitus management training. Br J Audiol 31:27–38CrossRefPubMedGoogle Scholar
  18. Erlandsson SI, Hallberg LR, Axelsson A (1992) Psychological and audiological correlates of perceived tinnitus severity. Int J Audiol 31:168–179CrossRefGoogle Scholar
  19. Erlandsson SI, Holgers KM (2001) The impact of perceived tinnitus severity on health-related quality of life with aspects of gender. Noise Health 3:39–51PubMedGoogle Scholar
  20. File SE, Seth P (2003) A review of 25 years of the social interaction test. Eur J Pharmacol 463:35–53CrossRefPubMedGoogle Scholar
  21. Fink JS, Smith GP (1980) Mesolimbicocortical dopamine terminal fields are necessary for normal locomotor and investigatory exploration in rats. Brain Res 199:359–384CrossRefPubMedGoogle Scholar
  22. Fitzpatrick D, Diamond IT, Raczkowski D (1989) Cholinergic and monoaminergic innervation of the cat’s thalamus: comparison of the lateral geniculate nucleus with other principal sensory nuclei. J Comp Neurol 288:647–675CrossRefPubMedGoogle Scholar
  23. Gage FH, Dunnett SB, Björklund A (1984) Spatial learning and motor deficits in aged rats. Neurobiol Aging 5:43–48CrossRefPubMedGoogle Scholar
  24. Gates GA, Mills JH (2005) Presbycusis. Lancet 366:1111–1120CrossRefPubMedGoogle Scholar
  25. Geyer MA (1995) Serotonergic functions in arousal and motor activity. Behav Brain Res 73:31–35CrossRefGoogle Scholar
  26. Goble T, Møller A, Thompson L (2009) Acute high-intensity sound exposure alters responses of place cells in hippocampus. Hear Res 253:52–59CrossRefPubMedGoogle Scholar
  27. Gould TD, Dao DT, Kovacsics CE (2009) The open field test. In: Gould TD (ed) Mood and anxiety related phenotypes in mice: characterization using behavioral tests. Humana Press, Totowa, p 1–20Google Scholar
  28. Guitton MJ (2009) Tinnitus-provoking salicylate treatment triggers social impairments in mice. J Psychosom Res 67:273–276CrossRefPubMedGoogle Scholar
  29. Hall IC, Sell GL, Chester EM, Hurley LM (2012) Stress-evoked increases in serotonin in the auditory midbrain do not directly result from elevations in serum corticosterone. Behav Brain Res 226:41–49CrossRefPubMedGoogle Scholar
  30. Hall IC, Sell GL, Hurley LM (2011) Social regulation of serotonin in the auditory midbrain. Behav Neurosci 125:501–511CrossRefPubMedPubMedCentralGoogle Scholar
  31. Hall IC, Rebec GV, Hurley LM (2010) Serotonin in the inferior colliculus fluctuates with behavioral state and environmental stimuli. J Exp Biol 213:1009–1017CrossRefPubMedPubMedCentralGoogle Scholar
  32. Hallberg LR, Erlandsson SI (1993) Tinnitus characteristics in tinnitus complainers and noncomplainers. Br J Audiol 27:19–27CrossRefPubMedGoogle Scholar
  33. Hesser H, Bankestad E, Andersson G (2015) Acceptance of tinnitus as an independent correlate of tinnitus severity. Ear Hear 36:e176–e182CrossRefPubMedGoogle Scholar
  34. Hiller W, Goebel G (2006) Factors influencing tinnitus loudness and annoyance. Arch Otolaryngol Head Neck Surg 132:1323–1330CrossRefPubMedGoogle Scholar
  35. Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54:21–30CrossRefPubMedGoogle Scholar
  36. Hurley LM, Thompson AM, Pollak GD (2002) Serotonin in the inferior colliculus. Hear Res 168:1–11CrossRefPubMedGoogle Scholar
  37. Husain FT, Schmidt SA (2014) Using resting state functional connectivity to unravel networks of tinnitus. Hear Res 307:153–162CrossRefPubMedGoogle Scholar
  38. Jacobs BL, Cohen A (1976) Differential behavioral effects of lesions of the medial or dorsal raphe nuclei in rats: open field and pain-elicited aggression. J Comp Physiol Psychol 90:102CrossRefPubMedGoogle Scholar
  39. Jakes SC, Hallam RS, Chambers C, Hinchcliffe R (1985) A factor analytical study of tinnitus complaint behaviour. Audiology 24:195–206CrossRefPubMedGoogle Scholar
  40. Jones A, May BJ (2016) Improving the reliability of tinnitus screening in laboratory animals. J Assoc Res Otolaryngol:1–13Google Scholar
  41. Katz RJ, Roth KA, Carroll BJ (1981) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5:247–251CrossRefPubMedGoogle Scholar
  42. Klepper A, Herbert H (1991) Distribution and origin of noradrenergic and serotonergic fibers in the cochlear nucleus and inferior colliculus of the rat. Brain Res 557:190–201CrossRefPubMedGoogle Scholar
  43. Kraus KS, Canlon B (2012) Neuronal connectivity and interactions between the auditory and limbic systems. Effects of noise and tinnitus. Hear Res 288:34–46CrossRefPubMedGoogle Scholar
  44. Kraus KS, Mitra S, Jimenez Z, Hinduja S, Ding D, Jiang H, Gray L, Lobarinas E, Sun W, Salvi RJ (2010) Noise trauma impairs neurogenesis in the rat hippocampus. Neuroscience 167:1216–1226CrossRefPubMedPubMedCentralGoogle Scholar
  45. Lauer AM, May BJ, Hao ZJ, Watson J (2009) Analysis of environmental sound levels in modern rodent housing rooms. Lab Anim (NY) 38:154–160CrossRefGoogle Scholar
  46. Leaver AM, Renier L, Chevillet MA, Morgan S, Kim HJ, Rauschecker JP (2011) Dysregulation of limbic and auditory networks in tinnitus. Neuron 69:33–43CrossRefPubMedPubMedCentralGoogle Scholar
  47. Li C, Zhang X, Hoffman HJ, Cotch MF, Themann CL, Wilson MR (2014) Hearing impairment associated with depression in US adults, National Health and Nutrition Examination Survey 2005-2010. JAMA Otolaryngol Head Neck Surg 140:293–302CrossRefPubMedPubMedCentralGoogle Scholar
  48. Lin FR, Yaffe K, Xia J, Xue Q, Harris TB, Purchase-Helzner E, Satterfield S, Ayonayon HN, Ferrucci L, Simonsick EM (2013) Hearing loss and cognitive decline in older adults. JAMA Intern Med 173:293–299CrossRefPubMedGoogle Scholar
  49. Liu L, Shen P, He T, Chang Y, Shi L, Tao S, Li X, Xun Q, Guo X, Yu Z, Wang J (2016) Noise induced hearing loss impairs spatial learning/memory and hippocampal neurogenesis in mice. Sci Rep 6:20374CrossRefPubMedPubMedCentralGoogle Scholar
  50. Lobarinas E, Sun W, Cushing R, Salvi R (2004) A novel behavioral paradigm for assessing tinnitus using schedule-induced polydipsia avoidance conditioning (SIP-AC). Hear Res 190:109–114CrossRefPubMedGoogle Scholar
  51. Manikandan S, Padma MK, Srikumar R, Parthasarathy NJ, Muthuvel A, Devi RS (2006) Effects of chronic noise stress on spatial memory of rats in relation to neuronal dendritic alteration and free radical-imbalance in hippocampus and medial prefrontal cortex. Neurosci Lett 399:17–22CrossRefPubMedGoogle Scholar
  52. Marriage J, Barnes N (1995) Is central hyperacusis a symptom of 5-hydroxytryptamine (5-HT) dysfunction? J Laryngol Otol 109:915–921CrossRefPubMedGoogle Scholar
  53. Mener DJ, Betz J, Genther DJ, Chen D, Lin FR (2013) Hearing loss and depression in older adults. J Am Geriatr Soc 61:1627–1629CrossRefPubMedPubMedCentralGoogle Scholar
  54. Naqvi F, Haider S, Perveen T, Haleem DJ (2012) Sub-chronic exposure to noise affects locomotor activity and produces anxiogenic and depressive like behavior in rats. Pharmacol Rep 64:64–69CrossRefPubMedGoogle Scholar
  55. Norena A, Cransac H, Chery-Croze S (1999) Towards an objectification by classification of tinnitus. Clin Neurophysiol 110:666–675CrossRefPubMedGoogle Scholar
  56. Pace E, Zhang J (2013) Noise-induced tinnitus using individualized gap detection analysis and its relationship with hyperacusis, anxiety, and spatial cognition. PLoS One 8:e75011CrossRefPubMedPubMedCentralGoogle Scholar
  57. Papesh MA, Hurley LM (2012) Plasticity of serotonergic innervation of the inferior colliculus in mice following acoustic trauma. Hear Res 283:89–97CrossRefPubMedGoogle Scholar
  58. Pattyn T, Van Den Eede F, Vanneste S, Cassiers L, Veltman DJ, Van De Heyning P, Sabbe BC (2016) Tinnitus and anxiety disorders: a review. Hear Res 333:255–265Google Scholar
  59. Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529CrossRefPubMedGoogle Scholar
  60. Pellow S, Chopin P, File SE, Briley M (1985) Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 14:149–167CrossRefPubMedGoogle Scholar
  61. Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463:3–33CrossRefPubMedGoogle Scholar
  62. Rauschecker JP, Leaver AM, Mühlau M (2010) Tuning out the noise: limbic-auditory interactions in tinnitus. Neuron 66:819–826CrossRefPubMedPubMedCentralGoogle Scholar
  63. Ropp TJ, Tiedemann KL, Young ED, May BJ (2014) Effects of unilateral acoustic trauma on tinnitus-related spontaneous activity in the inferior colliculus. J Assoc Res Otolaryngol 15(6):1007-1022Google Scholar
  64. Rygula R, Abumaria N, Flügge G, Fuchs E, Rüther E, Havemann-Reinecke U (2005) Anhedonia and motivational deficits in rats: impact of chronic social stress. Behav Brain Res 162(1):127–34Google Scholar
  65. Salchner P, Lubec G, Singewald N (2004) Decreased social interaction in aged rats may not reflect changes in anxiety-related behaviour. Behav Brain Res 151:1–8CrossRefPubMedGoogle Scholar
  66. Säljö A, Mayorga M, Bolouri H, Svensson B, Hamberger A (2011) Mechanisms and pathophysiology of the low-level blast brain injury in animal models. NeuroImage 54:S83–S88CrossRefPubMedGoogle Scholar
  67. Schwartzbaum J, Gay PE (1966) Interacting behavioral effects of septal and amygdaloid lesions in the rat. J Comp Physiol Psychol 61:59CrossRefPubMedGoogle Scholar
  68. Simpson JJ, Davies WE (2000) A review of evidence in support of a role for 5-HT in the perception of tinnitus. Hear Res 145:1–7CrossRefPubMedGoogle Scholar
  69. Slawecki CJ (2005) Comparison of anxiety-like behavior in adolescent and adult Sprague-Dawley rats. Behav Neurosci 119:1477CrossRefPubMedGoogle Scholar
  70. Soffié M, Bronchart M (1988) Age-related scopolamine effects on social and individual behaviour in rats. Psychopharmacology 95:344–350CrossRefPubMedGoogle Scholar
  71. Supple WF, Leaton RN, Fanselow MS (1987) Effects of cerebellar vermal lesions on species-specific fear responses, neophobia, and taste-aversion learning in rats. Physiol Behav 39:579–586CrossRefPubMedGoogle Scholar
  72. Svensson L, Ahlenius S (1983) Suppression of exploratory locomotor activity by the local application of dopamine or l-noradrenaline to the nucleus accumbens of the rat. Pharmacol Biochem Behav 19:693–699CrossRefPubMedGoogle Scholar
  73. Tambs K (2004) Moderate effects of hearing loss on mental health and subjective well-being: results from the Nord-Trøndelag Hearing Loss Study. Psychosom Med 66:776–782CrossRefPubMedGoogle Scholar
  74. Tyler RS, Baker LJ (1983) Difficulties experienced by tinnitus sufferers. J Speech Hear Disord 48:150–154CrossRefPubMedGoogle Scholar
  75. Valle FP (1970) Effects of strain, sex, and illumination on open-field behavior of rats. Am J Psychol:103–111Google Scholar
  76. Van Dijken HH, Tilders FJ, Olivier B, Mos J (1992) Effects of anxiolytic and antidepressant drugs on longlasting behavioural deficits resulting from one short stress experience in male rats. Psychopharmacology 109(4):395–402Google Scholar
  77. Walsh RN, Cummins RA (1976) The open-field test: A critical review. Psychol Bull 83(3):482Google Scholar
  78. Wang S, Yu Y, Feng Y, Zou F, Zhang X, Huang J, Zhang Y, Zheng X, Huang X, Zhu Y (2016) Protective effect of the orientin on noise-induced cognitive impairments in mice. Behav Brain Res 296:290–300CrossRefPubMedGoogle Scholar
  79. Welch D, Dawes PJ (2008) Personality and perception of tinnitus. Ear Hear 29:684–692CrossRefPubMedGoogle Scholar
  80. Willard F, Ho R, Martin G (1984) The neuronal types and the distribution of 5-hydroxytryptamine and enkephalin-like immunoreactive fibers in the dorsal cochlear nucleus of the North American opossum. Brain Res Bull 12:253–266CrossRefPubMedGoogle Scholar
  81. Yang G, Lobarinas E, Zhang L, Turner J, Stolzberg D, Salvi R, Sun W (2007) Salicylate induced tinnitus: behavioral measures and neural activity in auditory cortex of awake rats. Hear Res 226:244–253CrossRefPubMedGoogle Scholar
  82. Zheng Y, Hamilton E, McNamara E, Smith P, Darlington C (2011) The effects of chronic tinnitus caused by acoustic trauma on social behaviour and anxiety in rats. Neuroscience 193:143–153CrossRefPubMedGoogle Scholar

Copyright information

© Association for Research in Otolaryngology 2017

Authors and Affiliations

  • Amanda M. Lauer
    • 1
    Email author
  • Gail Larkin
    • 1
  • Aikeen Jones
    • 1
  • Bradford J. May
    • 1
  1. 1.Department of Otolaryngology-HNS and Center for Hearing and BalanceJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations