Demyelination in rat model of mania-like behavior

Abstract

Introduction

Ample amount of data suggests role of REM sleep deprivation as the cause and effect of mania. In the present model, we have tried to implement behavioral sensitization to sleep deprivation, conditions mimicking natural circumstances, so as to produce an animal model with symptomatology resembling very close to human mania. Pre-clinical and clinical studies have shown that mania is often co-morbid with multiple sclerosis, therefore we sought to find out whether myelin integrity is disrupted and if lithium could protect against such damage.

Objectives

(1) To analyse mania-like behavior after REM sleep deprivation. (2) To analyse any damage to myelin under TEM.

Aims

We wanted to see if there could be any damage to myelin after behavioral sensitization to stress.

Methods

Rats were sleep deprived by classical flowerpot or platform method. OFT was performed to assess behavior of rats. The analysis was performed over 5 min, separated into 5 bins of 1 min each. Behavioral scores included total square entries, inner square entries, time spent in center, rearing frequency, time spent rearing, number of grooming bouts, time spent grooming defecation and time spent still. TEM was performed to study changes in myelination in two distinct regions of brain, DG and VTA.

Results

It was observed that the REM sleep deprived rats had mania like symptoms. REM sleep deprivation lead to demyelination in DG and VTA. Lithium treatment restored myelination per se.

Conclusions

The result suggests the involvement of myelin damage in the pathogenesis of mania, Li offers protection against such damage.

Disclosure of interest

The authors have not supplied their declaration of competing interest.