To evaluate the addictive potential of 2-FDCK (20mg/kg) and KET (20mg/kg) in mice, we employed a standard conditioned place preference (CPP) paradigm. During the conditioning phase, mice learned to associate the abused drug reward with a specific contextual chamber. After a 21-day conditioning period, the mice were reintroduced to the CPP apparatus and allowed to freely explore both chambers in the absence of the drug. Subsequently, samples from the hippocampus, mPFC, and VTA were collected and pretreated. We also extracted primary neurons from the mouse prefrontal cortex as an in vitro model, exposed them to 2-FDCK or KET (30uM), and collected the samples. All samples were then analyzed using an Eksigent® M5+TripleTOF® 5600+ system. All data acquisition was performed using Analyst TF 1.7 software, and the IDA data were searched against the database using ProteinPilot™ software.