Chronic methylphenidate treatment during adolescence has long-term effects on monoaminergic function.




Journal Title

Journal ISSN


Volume Title





Peer reviewed



Background: Psychostimulants like methylphenidate or D-amphetamine are often prescribed for attention deficit and hyperactivity disorders in children. Whether such drugs can be administered into a developing brain without consequences in adulthood is still an open question. Methods: Here, using in vivo extracellular electrophysiology in anesthetised preparations, combined with behavioural assays, we have examined the long-term consequences in adulthood of a chronic methylphenidate oral administration (5 mg/kg/day, 15 days) in early adolescent (post-natal day 28) and late adolescent (post-natal day 42) rats, by evaluating body weight change, sucrose preference (indicator of anhedonia), locomotor sensitivity to D-amphetamine and electrical activities of ventral tegmental area dopamine and dorsal raphe nucleus serotonin neurons. Results: Chronic methylphenidate treatment during early or late adolescence did not induce weight deficiencies and anhedonia-like behaviours at adulthood. However, it increased bursting activities of dorsal raphe nucleus serotonin neurons. Furthermore, chronic methylphenidate treatment during early but not during late adolescence enhanced D-amphetamine-induced rearing activity, as well as ventral tegmental area dopamine cell excitability (firing, burst and population activity), associated with a partial desensitisation of dopamine D2 auto-receptors. Conclusions: We have demonstrated here that early, but not late, adolescent exposure to oral methylphenidate may induce long-lasting effects on monoamine neurotransmission. The possible clinical implication of these data will be discussed.


Original investigation showing potential long-term consequences of chronic psychostimulant administration in adolescence. The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.


Methylphenidate, adolescence, dopamine neurons, serotonin neurons, electrophysiology


Di Miceli, M., Omoloye, A. and Gronier, B. (2018) Chronic methylphenidate treatment during adolescence has long-term effects on monoaminergic function. Journal of Psychopharmacology, 33 (1), pp. 109-121


Research Institute

Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)