Gut Microbiota Analysis in Rats with Methamphetamine-Induced Conditioned Place Preference

Abstract

Methamphetamine abuse is a major public health crisis. Because accumulating evidence supports the hypothesis that the gut microbiota plays an important role in central nervous system (CNS) function, and research on the roles of the microbiome in CNS disorders holds conceivable promise for developing novel therapeutic avenues for treating CNS disorders, we sought to determine whether administration of methamphetamine leads to alterations in the intestinal microbiota. In this study, the gut microbiota profiles of rats with methamphetamine-induced conditioned place preference (CPP) were analyzed through 16S rRNA gene sequencing. The fecal microbial diversity was slightly higher in the METH CPP group. The propionate-producing genus Phascolarctobacterium was attenuated in the METH CPP group, and the family Ruminococcaceae was elevated in the METH CPP group. Short chain fatty acid analysis revealed that the concentrations of propionate were decreased in the fecal matter of METH-administered rats. These findings provide direct evidence that administration of METH causes gut dysbiosis, enable a better understanding of the function of gut microbiota in the process of drug abuse, and provide a new paradigm for addiction treatment.

Metabolomics analysis of serum in a rat heroin self-administration model undergoing reinforcement based on 1H-nuclear magnetic resonance spectra

“…The slowed GI motility disturbs the profiling of metabolites in the serum. In addition, heroin administration leads to an alteration in gut microbiota [ 36 ], and gut microbiota can in turn impact serum metabolites. Therefore, more well designed studies are needed to verify whether the observed changes in metabolites were caused by heroin reinforcement directly or were an indirect result mediated by gut motility/gut microbiota.…”

Berberine Facilitates Extinction of Drug-Associated Behavior and Inhibits Reinstatement of Drug Seeking

“…Although we have demonstrated that berberine facilitates the extinction of drug-associated behavior by enhancing consolidation of extinction memory, further studies are required to explore potential direct targets of berberine. A number of CNS diseases have been linked to abnormalities of gastrointestinal tract and recent studies suggest that gut microbiota plays a key role in the development of drug addiction (Kiraly et al, 2016;Ning et al, 2017;Meckel and Kiraly, 2019). Moreover, remarkable effects of berberine on gut microbiota and regulation of related disease pathophysiology have been recently reported (Cui et al, 2018;Feng et al, 2019;Yue et al, 2019).…”

Differences in Gut Microbial Diversity are Driven by Drug Use and Drug Cessation by Either Compulsory Detention or Methadone Maintenance Treatment

“…Xu et al (2017) reported that Ruminococcus OTUs were more abundant in DU compared to HC [33]. Ning et al (2017) also found that Ruminococcaceae were more abundant in rats with methamphetamine-induced conditioned place preference than in the control group [34]. Furthermore, high abundance of Ruminococcaceae was reported to have a positive relationship with anxiety but was inversely correlated with place memory [62], which negatively impacts cognitive function [34].…”

“…Ning et al (2017) also found that Ruminococcaceae were more abundant in rats with methamphetamine-induced conditioned place preference than in the control group [34]. Furthermore, high abundance of Ruminococcaceae was reported to have a positive relationship with anxiety but was inversely correlated with place memory [62], which negatively impacts cognitive function [34]. Thus, the high abundance of Ruminococcus in the gut may be connected to impaired memory and cognitive function for DU subjects, although any relationship between Ruminococcus and cognitive function would require closer scrutiny using isolated strains in a model system.…”

“…Xu et al (2017) showed that Prevotella, Ruminococcus, and Roseburia are found in higher abundance in patients with substance use disorders compared to healthy controls (HC) [33]. Characterization of gut microbiota in rats treated with methamphetamine showed that Ruminococcaceae and Bacillaceae were more abundant in the rats with methamphetamine-induced conditioned place preference compared with the control group [34]. Therefore, gut microbial diversity may be shaped by addiction-associated behaviors and these communities can potentially function as biological indicators to evaluate the health of people with a history of drug use, such as current, former, and recovering drug users.The Honghe Prefecture of Yunnan Province is a region notorious in China for the prevalence of drug use.…”