Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract

Abstract

Aims/Hypothesis: Tinnitus is a phantom sound perception affecting both auditory and limbic structures. The mechanisms of tinnitus remain unclear and it is debatable whether tinnitus alters attention to sound and the ability to inhibit repetitive sounds, a phenomenon also known as auditory gating. Methods: 22 male C57BL/6J mice were used in this study. Anesthetized mice were exposed to a 9-11 kHz narrow band noise (90 dBSPL for 1 hr) and sham exposed mice were used as controls. Hearing thresholds were measured using auditory brainstem responses (ABRs) and tinnitus was assessed using Gap prepulse inhibition of acoustic startle (GPIAS). After the induction of tinnitus, mice were implanted multi-electrodes to assess auditory event-related potentials (aERPs) in the dorsal hippocampus in response to paired clicks. Alterations of aERPs under nicotine (1.0 mg/kg, intraperitoneal (i.p.) or cannabis extract (100 mg/Kg, i.p.) were evaluated (in isolation or in combination), the latter containing 47.25 mg/kg of tetrahydrocannabinol (THC); 0.43 mg/kg of cannabidiol (CBD) and 1.17 mg/kg of cannabinol (CBN), as analyzed by high-performance liquid chromatography (HPLC). Saline-treated animals were used as controls. Results: Our results show that mice with behavioral evidence of tinnitus display auditory gating of repetitive click, but with larger amplitudes and longer latencies of the N40 component. In contrast, no difference was observed in the P80 amplitude and latency between groups or treatments. The combination of cannabis extract and nicotine also improved auditory gating ratio in mice with noise-induced tinnitus without permanent hearing threshold shifts by strongly increasing the first N40 click amplitude but without altering the second click response amplitude. Furthermore, the increased latency of the N40 component suggests altered temporal processing of triggered attention in mice with tinnitus due to an increased sensitivity to the exposure to cannabis extract. Conclusion/Interpretation: In summary, we show that nicotine and cannabis extract alter sensory gating in mice with behavioral evidence of tinnitus and propose that the altered central plasticity in tinnitus is more sensitive to the combined actions on the cholinergic and the endocannabinoid systems. We conclude that the limbic system may play a role in the altered sensory gating responses on tinnitus since the hippocampus responses to auditory inputs are altered. These findings could enable a new understanding of which neuronal pathways could be involved in sensory gating in tinnitus.

Alterations of auditory sensory gating in mice with noise-induced tinnitus treated with nicotine and cannabis extract

“…All plots were produced using Matplotlib (Hunter 2007), and schematics were done using Inkscape (Inkscape Project, 2022). All scripts used for recordings and analysis are available online (Ciralli et al, 2022).…”

Unraveling the role ofSlc10a4in auditory processing and sensory motor gating: implications for neuropsychiatric disorders?

“…Animals were assessed for deficits in sensory filtering using a paired-click paradigm for recording auditory evoked potentials (Siegel et al 2005; Bickel et al 2007; Ciralli et al 2022, pre-print ). Mice were placed in a standard plastic cage bottom inside a custom-built sound shielded chamber fitted with LED lights and a digital camera to record behavior.…”

“…Auditory ERP analysis was performed similarly to previously described (Ciralli et al, 2022, pre-print ). Before extracting auditory event-related potentials from the extracellular recordings, broken channels were identified for each animal and removed from further analysis.…”