Anxiety-like behavior induced by salicylate depends on age and can be prevented by a single dose of 5-MeO-DMT.

Abstract:

: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.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Winne J,Boerner BC,Malfatti T,Brisa E,Doerl J,Nogueira I,Leão KE,Leão RN

doi

10.1016/j.expneurol.2020.113175

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

113175

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(20)30007-8

journal_volume

326

pub_type

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