Methylphenidate exposure in juvenile period elicits locomotion changes and anxiolytic-like behavior in adulthood: Evidence using zebrafish as a translational model

Abstract

Methylphenidate (MPH) is a central nervous system stimulant that is mainly used for Attention-Deficit/Hyperactivity Disorder (ADHD). It is well known that there is a high rate of ADHD misdiagnosis, leading to a great number of neurotypical children chronically exposed to MPH in early periods of life. This increase raises concern about possible long-lasting effects of this exposure. We aimed to evaluate whether exposure to MPH during childhood might impact adult behavioral pattern. For this purpose, we used zebrafish as a translational model considering its robustness as experimental model and fast life cycle. Fish were exposed during juvenile period (from 30 to 60 post-natal day) at MPH therapeutic concentration (2 mg L−1), and behavioral tests were performed at fish adulthood (120 post-natal day). MPH provoked slight anxiolytic-like effects and hyperlocomotion, and no differences on sociability and cortisol levels were observed. Moreover, sex did not affect any of the parameters evaluated. These results demonstrate that early chronic exposure to MPH leads to neurobehavioral adaptations that persist into adulthood in zebrafish regardless of sex, suggesting that the misuse of MPH during childhood and adolescence can alter neurobehavioral plasticity and these alterations might persist until adulthood.