In previous studies, the environmental endocrine disruptor (EED) bisphenol A was shown to enhance morphine- or methamphetamine-induced addictive states in rodents. Furthermore, prenatal or postnatal exposure to EEDs, such as phthalates or bisphenol A, has been associated with neurobehavioral disorders, including autism and ADHD. Recent studies have also reported that individuals with ADHD exhibit higher rates of nicotine dependence compared to controls. Based on these findings, the present study investigated the effect of materal exposure to di-(2-methoxyethyl) phthalate (DMEP) on susceptibliltiy to nicotine-induced locomotor sensitization in the adult offspring rats. We found that maternal exposure to DMEP did not alter baseline locomotor activity in either male or female adult offsrping compared with materal saline-exposed group. However, repeated administration of nicotine induced a greater development and expression of locomotor sensitization in adult male offspring maternally exposed to DMEP than in those exposed to saline. In contrast, no significant differences in the development or expression of locomotor sensitization were observed in female offspring between the DMEP- and saline-exposed group. Moreover, dopamine (DA) D1 receptor, but not D2 receptor, mRNA levels were evaluated in the dorsal striatum of adult male offsrping maternally exposed to DMEP compared with controls, and pharmacological blockade of DAD1 receptor attenuated the expression of locomotor sensitization by nicotine challenge in this group. Taken together, thses findings suggest that maternal DMEP exposure may enhance susceptibility to nicotine dependence in adult male offsrping, potentially through upregulation of DAD1 receptor in the dorsal striatum. 

Acknowledgements: This research was supported by grants from the National Research Foundation of Korea funded by Korea government (MIST) (2021R1A2C1009755, RS-2025-00520266) and the Korea Institute of Toxicology (2710086923).