Experimental neurologyJan 11, 2020

Salicylate causes anxiety-like behavior that varies with age and may be stopped by one dose of 5-MeO-DMT

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Updated Mar 29, 2026

Abstract

Anxiety-like behavior and increased theta oscillations occur only in young mice following salicylate treatment.

Salicylate intoxication is linked to tinnitus and anxiety in humans.
In young mice, a single dose of salicylate (300 mg/kg) leads to anxiety-like behavior and increased theta oscillations in the hippocampus.
Older mice do not exhibit anxiety-like behavior or increased theta oscillations after salicylate treatment.
Increased theta and slow gamma oscillations are observed in the ventral hippocampus and medial prefrontal cortex during anxiety tests following salicylate administration.
Pre-treatment with a single dose of the hallucinogenic compound 5-MeO-DMT prevents anxiety-like behavior and oscillation increases after salicylate injection in young mice.

Simplified

Salicylate intoxication is a cause of tinnitus and comorbidly associated with anxiety in humans. In a previous work, we showed that salicylate induces anxiety-like behavior and hippocampal type 2 theta oscillations (theta2) in mice. Here we investigate if the anxiogenic effect of salicylate is dependent on age and previous tinnitus experience. We also tested whether a single dose of DMT can prevent this effect. Using microwire electrode arrays, we recorded local field potential in young (4-5- month-old) and old (11-13-month-old) mice to study the electrophysiological effect of tinnitus in the ventral hippocampus (vHipp) and medial prefrontal cortex (mPFC) in an open field arena and elevated plus maze 1h after salicylate (300mg/kg) injection. We found that anxiety-like behavior and increase in theta2 oscillations (4-6 Hz), following salicylate pre-treatment, only occurs in young (normal hearing) mice. We also show that theta2 and slow gamma oscillations increase in the vHipp and mPFC in a complementary manner during anxiety tests in the presence of salicylate. Finally, we show that pre-treating mice with a single dose of the hallucinogenic 5-MeO-DMT prevents anxiety-like behavior and the increase in theta2 and slow gamma oscillations after salicylate injection in normal hearing young mice. This work further support the hypothesis that anxiety-like behavior after salicylate injection is triggered by tinnitus and require normal hearing. Moreover, our results show that hallucinogenic compounds can be effective in treating tinnitus-related anxiety.

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Declaration of Competing Interest The authors declare no conflict of interest.

PubMed

Salicylate causes anxiety-like behavior that varies with age and may be stopped by one dose of 5-MeO-DMT

Abstract

Full Text

Funding

Competing interests

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