New psychoactive substances that have been modified and developed to mimic the effects of already prohibited drugs are an increasingly global problem. Among them, 2-(2,5-dimethoxy-4-nitrophenyl)-N-(2-methoxybenzyl)ethanamine (25 N-NBOMe) belonging to the N-methoxybenzyl-phenethylamines (NBOMes) class has recently emerged as a new psychoactive substance. However, the rewarding effects of 25 N-NBOMe have not yet been studied. Here, we investigated the addictive potential of 25 N-NBOMe using conditioned place preference and self-administration in rodents. We also evaluated the effects of 25 N-NBOMe on the dopaminergic system using Western blot analysis. We found that 25 N-NBOMe at 3 mg/kg significantly increased conditioned place preference in mice and 25 N-NBOMe at 0.01 mg/kg/infusion significantly enhanced self-administration in rats. In addition, repeated administration of 25 N-NBOMe did not affect the expression of the dopamine 1 receptor but significantly reduced the expression of the dopamine 2 receptor in both the nucleus accumbens (NAc) and the dorsal striatum (DSt). We also found that 25 N-NBOMe significantly decreased the expression of the dopamine transporter only in the NAc, while increasing the expression of the phosphorylated dopamine transporter in both the NAc and the DSt. Furthermore, 25 N-NBOMe significantly reduced the expression of tyrosine hydroxylase in the NAc but not in the DSt. Taken together, these findings suggest that 25 N-NBOMe has abuse potential via dopaminergic system.