{Reference Type}: Journal Article
{Title}: Rhynchophylline inhibits methamphetamine dependence via modulating the miR-181a-5p/GABRA1 axis.
{Author}: Jiang MJ;Li J;Luo CH;Zhu C;Chen ZJ;Bai W;Hu TY;Feng CH;Li C;Mo ZX;
{Journal}: J Ethnopharmacol
{Volume}: 314
{Issue}: 0
{Year}: 2023 Oct 5
{Factor}: 5.195
{DOI}: 10.1016/j.jep.2023.116635
{Abstract}: <B>BACKGROUND: </B>Uncaria rhynchophylla (Miq.) Miq. ex Havil. is a plant species that is routinely devoted in traditional Chinese medicine to treat central nervous system disorders. Rhynchophylline (Rhy), a predominant alkaloid isolated from Uncaria rhynchophylla (Miq.) Miq. ex Havil., has been demonstrated to reverse methamphetamine-induced (METH-induced) conditioned place preference (CPP) effects in mice, rats and zebrafish. The precise mechanism is still poorly understood, thus further research is necessary.<BR><B>OBJECTIVE: </B>This study aimed to investigate the role of miRNAs in the inhibitory effect of Rhy on METH dependence.<BR><B>METHODS: </B>A rat CPP paradigm and a PC12 cell addiction model were established. Microarray assays were used to screen and identify the candidate miRNA. Behavioral assessment, real-time PCR, dual-luciferase reporter assay, western blotting, stereotaxic injection of antagomir/agomir and cell transfection experiments were performed to elucidate the effect of the candidate miRNA and intervention mechanism of Rhy on METH dependence.<BR><B>RESULTS: </B>Rhy successfully reversed METH-induced CPP effect and the upregulated miR-181a-5p expression in METH-dependent rat hippocampus and PC12 cells. Moreover, suppression of miR-181a-5p by antagomir 181a reversed METH-induced CPP effect. Meanwhile, overexpression of miR-181a-5p by agomir 181a in combination with low-dose METH (0.5 mg/kg) elicited a significant CPP effect, which was blocked by Rhy through inhibiting miR-181a-5p. Finally, the result demonstrated that miR-181a-5p exerted its regulatory role by targeting γ-aminobutyric acid A receptor α1 (GABRA1) both in vivo and in vitro.<BR><B>CONCLUSIONS: </B>This finding reveals that Rhy inhibits METH dependence via modulating the miR-181a-5p/GABRA1 axis, which may be a promising target for treatment of METH dependence.