MiR-222-3p regulates methamphetamine-induced behavioral sensitization through PP2A–AKT signaling pathway in the dorsal striatum of male mice

Drug addiction is a chronic and recurrent brain disease. Our previous research demonstrated that the B subunit of phosphatase 2A (PP2A/B) increased in the dorsal striatum (DS) of methamphetamine (METH)-sensitized mice. Interestingly, studies indicate that PP2A/B can also interplay with microRNA (miRNA). In this study, we investigated seven miRNAs that have been reported to potentially interplay with PP2A/B, and our results showed that miR-222-3p significantly decreased in the DS of METH-sensitized mice. We further used dual-luciferase reporter assay to clarify the regulatory relationship between miR-222-3p and PP2A/B mRNA, and we also constructed adeno-associated virus (AAV) to overexpress miR-222-3p in the DS to further examine the influence of miR-222-3p on METH-induced behavioral sensitization. Our results demonstrated that miR-222-3p did interplay with PP2A/B mRNA and overexpressed miR-222-3p could significant attenuate METH-induced behavioral sensitization. At the same time, overexpressed miR-222-3p could reverse the change in the PP2A–AKT signaling pathway in the DS of METH-sensitized mice. Our results indicate that overexpression of miR-222-3p in the DS might attenuate METH-induced behavioral sensitization through the PP2A–AKT signaling pathway.