The prevalence of attention-deficit/hyperactivity disorder (ADHD), one of the most common neurodevelopmental disorders, in adults is estimated to be about 5%, and the number of prescriptions is increasing. However, the transgenerational effects of methylphenidate (MPH), a first-line drug of ADHD, are unclear. Recently, it has been reported that paternal environmental factors induce epigenetic changes that affect the neurodevelopment of children and grandchildren. Therefore, we investigated the effects of paternal MPH administration on the next (F1) and subsequent generations (F2) in the mice model.
Male ICR mice (6 weeks old) were administered MPH or saline for 21 days and mated with female mice to obtain F1. At nine weeks of age, F1 males were mated with female mice to obtain F2. At six weeks of age, both F1 and F2 were subjected to the elevated plus maze test to assess impulsivity. Additionally, total RNA from the striatum of F1 and F2 was subjected to RNA-seq, and the enrichment analysis was conducted.
Both F1 and F2 of MPH groups significantly increased impulsivity. Enrichment analysis showed an enrichment of exocytosis-related genes involved in neurotransmission in both F1 and F2. These findings suggest that MPH administration to male mice may alter behavior by affecting neurofunction in the next and subsequent generations.