A novel microRNA, novel-m009C, regulates methamphetamine rewarding effects

Abstract

Methamphetamine (METH) is a widely abused psychostimulant, whose hyper-rewarding property is believed to underlie its addictive effect, but the molecular mechanism regulating this effect remains unclear. We previously reported that decreased expression of a novel microRNA (miRNA), novel-m009C, is implicated in the regulation of METH hyperlocomotion. Here, we found that novel-m009C may be homologous to hsa-miR-604. Its expression is consistently downregulated in the nucleus accumbens (NAc) of mice when exposed to METH and cocaine, whereas significant alterations in novel-m009C expression were not observed in the NAc of mice subjected to other rewarding and psychiatric stimuli, such as sucrose, morphine and MK-801. We further found the substantial reduction in novel-m009C expression may be regulated by both dopamine receptor D1 (D1R) and D2 (D2R). Increasing novel-m009C levels in the NAc attenuated METH-induced conditioned place preference (CPP) and hyperlocomotion, whereas inhibiting novel-m009C expression in the NAc enhanced these effects but did not change the preference of mice for a natural reward, i.e., sucrose. These effects may involve targeting of genes important for the synaptic transmission, such as Grin1 (NMDAR subunit 1). Our findings demonstrate an important role for NAc novel-m009C in regulating METH reward, reveal a novel molecular regulator of the actions of METH on brain reward circuitries and provide a new strategy for treating METH addiction based on the modulation of small non-coding RNAs.

Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine‐induced gut microbiota dysbiosis

“…Therefore, it is urgent to develop safe and effective therapeutic drugs. MA is a kind of psychomotor stimulant and has been reported to induce a strong rewarding effect [7]. In this study, we observed that LBP could reverse MA‐induced high CPP scores and behavioral sensitization.…”

“…Conditioned place preference (CPP) is a commonly used behavior test to evaluate the reward-effect mechanism of addictive drugs [6]. Most studies use the CPP test to study drug addiction mechanisms and screen potential drug strategies to inhibit relapse [7,8]. Prevention of drug relapse is a primary condition in the treatment of drug addiction, and it is also a research hotspot in recent years.…”

Identification of the circRNA–miRNA–mRNA network for treating methamphetamine‐induced relapse and behavioral sensitization with cannabidiol

“…In recent years, non-coding RNAs (ncRNAs) have become an important biomarker for studying the pathogenesis of disease and identifying drug targets. [14][15][16][17] ncRNAs, such as miRNAs, silence gene expression by binding to mRNA, thereby affecting the function of organisms. Conversely, the long ncRNAs (lncRNAs) and circular RNAs (circRNAs) can competitively bind miRNAs as competing endogenous RNAs (ceRNAs) to regulate the downstream gene expressions, which plays a positive role in disease treatment.…”

“…In recent years, non‐coding RNAs (ncRNAs) have become an important biomarker for studying the pathogenesis of disease and identifying drug targets 14–17 . ncRNAs, such as miRNAs, silence gene expression by binding to mRNA, thereby affecting the function of organisms.…”

Effect of aerobic exercise on brain metabolite profiles in mice models of methamphetamine addiction: LC-MS-based metabolomics study

“…In the eld of drug addiction, conditioned place preference(CPP) is an effective and commonly used method to verify drug dependence status through behavioral changes in animals [38,39]. Changes in CPP caused by MA abuse can be mapped to multiple brain regions such as the nucleus accumbens [40], hippocampus [41], and hypothalamus [42], and are also associated with changes in the trends of addiction-related neurotransmitters such as dopamine and glutamate [43,44]. Based on the above evidence, we hypothesize that exercise can modulate the metabolic homeostasis of the MA-induced brain.…”