4-Methylmehtylphenidate (4-MMP) is a novel psychoactive substance (NPS) which is an analog of methylphenidate (MPH), known for its amphetamine-like properties and global misuse. However, its addictive characteristics and pharmacological profile remain incompletely understood. Here, we evaluated the addictive potential of 4-MMP using conditioned place preference (CPP) and behavioral sensitization (BS) tests in mice. We explored the dopaminergic involvement by administering dopamine (DA) receptor antagonists (SCH23390 and haloperidol) during CPP and chemogenetically inhibiting medium spiny neurons (MSNs) expressing dopamine D1 receptors (D1DR) in the nucleus accumbens (NAc) in separate cohorts. In vitro assays were conducted to evaluate the DA transporter (DAT) inhibition potency of 4-MMP. Also, we measured DA concentration, DA-related protein expression in the NAc, and quantified DA neuronal activation in the ventral tegmental area (VTA) by analyzing c-fos immunoreactive cells. Our findings revealed that 4-MMP administration significantly increased CPP, induced BS, and exhibited bidirectional cross-sensitization with methamphetamine. SCH23390 exclusively blocked 4-MMP induced CPP, while inhibition of D1-MSNs by clozapine (CNO) stimulation of Gi-DREADD prevented the expression of 4-MMP CPP. 4-MMP exhibited >10-fold stronger DAT inhibition than methamphetamine in HEK-293 cells. Moreover, 4-MMP treatment elevated DA levels, D1DR and p-CREB/CREB expression levels in the NAc, and increased c-fos expression in VTA DA neurons. These findings suggest that 4-MMP may induce abuse potential in mice by affecting the dopaminergic system accompanied by neural plasticity. (Supported by grant from Ministry of Food and Drug Safety 23212MFDS218)