Chronic Lithium Treatment Affects Anxious Behaviors and theExpression of Serotonergic Genes in Midbrain Raphe Nuclei of Defeated Male Mice

Dmitry A Smagin,Irina V Belozertseva,Nikolay V Tamkovich,Irina L Kovalenko,Natalia N Kudryavtseva,Anna G Galyamina,Konstantin O Baranov

doi:10.3390/biomedicines9101293

Abstract

There is experimental evidence that chronic social defeat stress is accompanied by the development of an anxiety, development of a depression-like state, and downregulation of serotonergic genes in midbrain raphe nuclei of male mice. Our study was aimed at investigating the effects of chronic lithium chloride (LiCl) administration on anxiety behavior and the expression of serotonergic genes in midbrain raphe nuclei of the affected mice. A pronounced anxiety-like state in male mice was induced by chronic social defeat stress in daily agonistic interactions. After 6 days of this stress, defeated mice were chronically treated with saline or LiCl (100 mg/kg, i.p., 2 weeks) during the continuing agonistic interactions. Anxiety was assessed by behavioral tests. RT-PCR was used to determine Tph2, Htr1a, Htr5b, and Slc6a4 mRNA expression. The results revealed anxiolytic-like effects of LiCl on social communication in the partition test and anxiogenic-like effects in both elevated plus-maze and social interaction tests. Chronic LiCl treatment upregulated serotonergic genes in midbrain raphe nuclei. Thus, LiCl effects depend on the treatment mode, psycho-emotional state of the animal, and experimental context (tests). It is assumed that increased expression of serotonergic genes is accompanied by serotonergic system activation and, as a side effect, by higher anxiety.

Highlights

Introduction iationsLithium salts are widely used in psychiatric practice in monotherapy regimens as mood stabilizers [1,2,3,4], in the supportive therapy of psycho-emotional disorders [5], and in the prevention of suicidal behaviors in patients [6,7,8]
We provide experimental data on the impact of chronic treatment with lithium chloride (LiCl) on the anxiety-like state caused by chronic social defeat stress that leads to a mixed anxiety/depression-like state in male mice [24,25,26]
There is th and defeated male mice in the social interaction test, we found that mice of possibility that may into havesubgroups a protective impact, to those in thetoelevated plus one group can be saline subdivided according to similar differential sensitivity

Summary

Introduction

Lithium salts are widely used in psychiatric practice in monotherapy regimens as mood stabilizers [1,2,3,4], in the supportive therapy of psycho-emotional disorders [5], and in the prevention of suicidal behaviors in patients [6,7,8]. Relapses in schizophrenia with aggressive or suicidal behavior, convulsions, and other health problems [13,14,15,16]. According to these studies, in clinical practice, patients with bipolar disorder demonstrate two types of lithium responsiveness: they are either good or poor responders. Lithium as monotherapy or in combination with other drugs is effective in 60% of chronically treated patients, but the treatment response remains heterogeneous and a large number of patients require a change in treatment after several weeks or months.

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