Conclusions
This study indicates that METH induces DA release via the DRD1-MeCP2-BDNF-TrkB signaling pathway. Furthermore, CBD significantly inhibits DA release induced by METH through modulation of this pathway.
Results
METH (400 μM) significantly increased DA release from primary neurons in vitro, which was blocked by CBD (1 μM) pretreatment. METH (400 μM) significantly increased the expression levels of DRD1, BDNF, and TrkB, but decreased the expression of MeCP2 in the neurons, whereas CBD (1 μM) pretreatment notably inhibited the protein changes induced by METH. In addition, DRD1 antagonist SCH23390 (10 μM) inhibited the DA release and protein change induced by METH in vitro. However, DRD1 agonist SKF81297 (10 μM) induced DA release and protein change in vitro, which was also blocked by CBD (1 μM) pretreatment. METH (2 mg/kg) significantly increased the DA level in the nucleus accumbens (NAc) of rats with activation of the DRD1-MeCP2-BDNF-TrkB signaling pathway, but these changes were blocked by CBD (40 or 80 mg/kg) pretreatment. Conclusions: This study indicates that METH induces DA release via the DRD1-MeCP2-BDNF-TrkB signaling pathway. Furthermore, CBD significantly inhibits DA release induced by METH through modulation of this pathway.