Korean Red Ginseng inhibits methamphetamine addictive behaviors by regulating dopaminergic and NMDAergic system in rodents

Abstract

Background Methamphetamine (METH) is the most widely used psychostimulant and has been known to exhibit reinforcing effects even after long abstinence. We showed the inhibitory effect of Korean Red Ginseng extract (RGE) on METH-induced addictive behaviors in animal models mimicking the human drug-use pattern. Methods We first investigated the effect of RGE on the acquisition of METH-induced dependence using self-administration and conditioned place preference (CPP) tests. Additionally, further experiments such as METH-induced motivational behavior and seeking behavior were conducted. To study the underlying mechanism, dopamine receptor, dopamine transporter, and N-methyl-D-aspartate receptor were assessed through Western blot analysis. Results Treatment with RGE significantly reduced METH-induced self-administration on a fixed-ratio 1 schedule of reinforcement. It could be also decreased a progressive ratio schedule, and inhibited METH-primed reinstatement. In CPP, RGE significantly prevented the development of METH-induced CPP. Moreover, RGE not only shortened the withdrawal period clearly, but also prevented the reinstatement of CPP. RGE treatment also reversed METH-induced overexpression of dopamine transporter, dopamine receptor D1, and NMDA receptor in the nucleus accumbens. Conclusion Our findings reflect that RGE has therapeutic potential to suppress METH-induced addictive behaviors by regulating dopaminergic and NMDAergic system.

Transient receptor potential ankyrin 1 channel modulates the abuse‐related mechanisms of methamphetamine through interaction with dopamine transporter

“…Moreover, METH increased the expression of proteins related to dopamine function, including DAT, which is responsible for dopamine clearance, TH, the dopamine synthetase, and the D 1 (D 1 receptor) and the D 2 -dopamine receptors (D 2 receptor), which mediate dopamine signalling, only in WT but not in TRPA1 KO mice. Overexpression of these proteins may be a compensatory mechanism for METH-induced overactivation of the dopamine system, as shown in previous rodent studies (Chauhan et al, 2014;Fibiger & McGeer, 1971;Lee et al, 2021;Thompson et al, 2015) and in patients with METH use disorder (Worsley et al, 2000). The present studies also showed that METH increased PKA and PKC expression only in WT mice.…”