Tinnitus-provoking salicylate treatment triggers social impairments in mice

Guitton, Matthieu J.

doi:10.1016/j.jpsychores.2008.10.017

Cited by 14 publications

(9 citation statements)

References 25 publications

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“…Such alterations clearly add to the burden of tinnitus on the patients and their families, and strongly impair the professional activities of the sufferers. Similar effects have been demonstrated in animals, using standardized assessment of social behavior (Guitton et al, 2008; Guitton, 2009). When perceiving tinnitus, animals exhibit striking alterations of their social behavior: tinnitus-perceiving animals actively seek inter-individual contact, but once the social interactions are initiated, they are unable to sustain them (Guitton, 2009).…”

Section: Mechanisms Of Tinnitussupporting

confidence: 70%

“…Understanding of the system dynamics in tinnitus pathophysiology, particularly the limbic component of tinnitus maintenance, allows for the development of more complex combined pharmacological strategies, as suggested earlier (Guitton et al, 2005; Guitton, 2006, 2009). Indeed, one of the most promising ways to cure tinnitus is the development of “hybrid” approaches, combining one specific pharmacological agent aimed at the causal mechanisms of tinnitus and acting on the abnormal neurotransmission in the cochlea with a second less specific pharmacological agent aimed at the symptoms, and regulating the abnormal neuromodulation in centralized neural networks (Figure 3).…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

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Tinnitus: pathology of synaptic plasticity at the cellular and system levels

Guitton¹

2012

Front. Syst. Neurosci.

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Despite being more and more common, and having a high impact on the quality of life of sufferers, tinnitus does not yet have a cure. This has been mostly the result of limited knowledge of the biological mechanisms underlying this adverse pathology. However, the last decade has witnessed tremendous progress in our understanding on the pathophysiology of tinnitus. Animal models have demonstrated that tinnitus is a pathology of neural plasticity, and has two main components: a molecular, peripheral component related to the initiation phase of tinnitus; and a system-level, central component-related to the long-term maintenance of tinnitus. Using the most recent experimental data and the molecular/system dichotomy as a framework, we describe here the biological basis of tinnitus. We then discuss these mechanisms from an evolutionary perspective, highlighting similarities with memory. Finally, we consider how these discoveries can translate into therapies, and we suggest operative strategies to design new and effective combined therapeutic solutions using both pharmacological (local and systemic) and behavioral tools (e.g., using tele-medicine and virtual reality settings).

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Section: Mechanisms Of Tinnitussupporting

confidence: 70%

Section: Therapeutic Implicationsmentioning

confidence: 99%

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

Guitton¹

2012

Front. Syst. Neurosci.

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“…Nonetheless, Karlsson et al ( 2009 ) also found that PPI was not affected in GLAST KO mice and hence reasoned that these mice display some of the multiple and complex symptoms belonging to schizophrenia (e.g., GLAST KO mice would belong to a subgroup of schizophrenia of lesser severity). Salicylate, which is known to be anxiogenic in high doses (Puel and Guitton, 2007 ; Guitton, 2009 ), exacerbated this anxiety effect by increasing startle amplitude responses in KO animals (Figure 3A ), something that we were able to qualitatively observe when handling the animals. It is thus possible that the higher basal anxiety levels of GLAST KO mice facilitated the tinnitus-inducing effects of salicylate, thereby increasing tinnitus intensity.…”

Section: Discussionmentioning

confidence: 57%

GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus

Patil

Han

et al. 2016

Front. Behav. Neurosci.

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Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.

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“…The perception of tinnitus leads to significant disturbances of social behaviour [19, 23, 49], which have been replicated in animal models [50]. In virtual settings, patients can confront distressing social situations and manage their emotional and behavioral responses under the control of a therapist, without having to face actual deleterious consequences or the related social stress.…”

Section: Virtual Reality-enhanced Behavioral Therapiesmentioning

confidence: 99%

Telemedicine in Tinnitus: Feasibility, Advantages, Limitations, and Perspectives

Guitton

2013

ISRN Otolaryngology

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Given the important patient needs for support and treatment, telemedicine—defined by medical approaches supported by the new technologies of information—could provide interesting alternative in tinnitus treatment. By analyzing the published tools and approaches which could be used in the context of telemedicine for tinnitus by health professionals or self-administrated by patients, this review summarizes, presents, and describes the principal telemedicine approaches available presently or in the near future to help assess or treat tinnitus or to offer support to tinnitus sufferers. Several pieces of evidence strongly support the feasibility of telemedicine approaches for tinnitus. Telemedicine can be used to help tinnitus sufferers at several points in the therapeutic process: for early screening, initial evaluation, and diagnosis; for optimizing therapeutic tools, particularly behavioural therapies and virtual reality-enhanced behavioral therapies; for long-term monitoring of patients and provision of online support. Several limitations are, however, discussed in order to optimize the safe development of such approaches. Cost effective and easy to implement, telemedicine is likely to represent an important part of the future of tinnitus therapies and should be progressively integrated by otolaryngologists.

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Tinnitus-provoking salicylate treatment triggers social impairments in mice

Cited by 14 publications

References 25 publications

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

Tinnitus: pathology of synaptic plasticity at the cellular and system levels

GLAST Deficiency in Mice Exacerbates Gap Detection Deficits in a Model of Salicylate-Induced Tinnitus

Telemedicine in Tinnitus: Feasibility, Advantages, Limitations, and Perspectives

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