Exercise-Regulated Gene Differential Expression In The Hippocampal Region of C57BL/6J Mice Ameliorates Methamphetamine Dependence

Abstract

Background: Methamphetamine (METH) is the highly addictive psychoactive drug which could harm to individual health and lead to great social problems. Various approaches have been adopted to address these problems, but relapse rates remain high. Recently, it has been found that comprehensive treatment combined with scientific and appropriate exercise intervention can improve mental state and physical fitness of drug addicts and promote their physical and mental rehabilitation. Long-term regular exercise improves the symptoms of METH withdrawal and reduce METH relapse. This study is to investigate the effects and regulated genes expression related to running exercise in METH addicted mice. Method: We used male C57BL/6J mice to construct METH addiction model and performed running exercise intervention, conditional place preference (CPP) was used to measure the effects of running intervention on METH addict mice. RNA sequencing(RNA-seq) and transcriptome analysis was performed on mice hippocampus, functions and differential expressed genes (DEGs) significantly regulated by exercise intervention in METH addict mice were analysed and noted.Results: The results showed that days of CPP preference was shortened to day 3 in METH addict mice given moderate exercise intervention, compared to preference to day 6 in METH addict mice without exercise. In addition, hippocampal transcriptome analysis revealed 12 DEGs significantly regulated by exercise intervention. By performing Gene ontology and KEGG analysis, function of immune responses was significant enriched in METH addiction mice with exercise. The expression of 12 differential expressed genes was verified by qRT-PCR, which showed that relative mRNA expression of DEGs was consistent with the RNA sequencing results.Conclusion: Running intervention can promote the recovery of METH addiction in mice, and the 12 candidate DEGs from mice hippocampus could use for further research on regulation mechanisms of exercise in METH addiction mice.