Host: The Japanese Society of Toxicology
Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by inattention, hyperactivity, and impulsivity. The number of prescriptions for ADHD patients is increasing, suggesting that the number of fertile women use such medication might also be increasing. However, the effects of MPD, the first-line drug for ADHD, on offspring have not been well examined. The purpose of this study was to clarify the effects of MPD exposure during the fetal period.
Dams were administered either water or MPD during pregnancy. Obtained male offspring were subjected to measurement of the locomotor activity and the elevated plus-maze test at 6 weeks old. Approximately 1/3 of the offspring were subjected to locomotor activity test after therapeutic treatment with MPD. The other 1/3 of the offspring were subjected to elevated plus-maze test after atomoxetine (ATX) treatment. The brains were collected from remaining offspring, gene expressions were determined by quantitative RT-PCR.
MPD-offspring showed an increase in the locomotor activity, which was suppressed by MPD treatment. The number of open arm entries, the time spent in open arms, and distance traveled in open arms were significantly increased in the MPD-offspring. This impulsivity was suppressed by ATX, another medication for ADHD, which a different action of the mechanism. MPD-offspring showed decreased Drd2 and Slc6a3 expression levels, which are often observed in ADHD model animals. Our results suggest that continuous use of MPD during pregnancy induces ADHD phenotypes in the offspring.
