Driving under the influence of MDMA increases the risk of car accidents and traumatic brain injury (TBI). In mice, a low dose of MDMA given one hour before a mild TBI normalized injury-induced changes in the dopamine system: it restored tyrosine hydroxylase (TH) levels and lowered elevated dopamine D2 receptor levels. Brain-derived neurotrophic factor (BDNF) levels rose only in mice that received both MDMA and mTBI. Haloperidol reversed the protective behavioral effect of MDMA. The findings suggest that normalizing TH and D2 signaling may alleviate cognitive deficits after TBI, though the protective agent here is an illegal drug.
Ketamine, originally developed as an anesthetic, is now being studied for depression treatment, but its addictive potential is a growing concern. This research used a mouse model of ketamine-induced conditioned place preference (CPP) to investigate changes in the striatum, a brain region involved in reward. Advanced metabolomics techniques revealed that ketamine abuse alters striatal metabolites, affecting pathways related to arginine synthesis, purine metabolism, and morphine addiction. Specifically, ketamine increased the neurotransmitter kynurenine (Kyn) and decreased dopamine (DA) in the striatum. These disturbances in Kyn and DA metabolism may underlie the addictive behaviors seen in the CPP model, offering new insights into ketamine addiction mechanisms.