Daily methylphenidate administration attenuates c-fos expression in the striatum of prepubertal rats

Neuroreport. 2003 Apr 15;14(5):769-72. doi: 10.1097/00001756-200304150-00022.


Methylphenidate (Ritalin) is a psychostimulant drug used to treat children with attention deficit hyperactivity disorder. Despite its widespread and increasing clinical use, little is known about the long-term consequences of drug treatment. We compared the effects of a single injection of methylphenidate with that of long-term methylphenidate injections (one/day; 14 days) on immediate-early gene expression (c-fos) in the striatum of prepubertal male rats. Rats (25 days old) were injected once daily for 14 days with either saline or methylphenidate (1, 2 or 10 mg/kg), or for 13 days with saline followed by one injection of methylphenidate (1, 2 or 10 mg/kg) on day 14, and were sacrificed 2 h post-injection. Methylphenidate dose-dependently increased FOS immunoreactivity in the striatum. A single injection of methylphenidate (2 or 10 mg/kg) on day 14, following saline treatment for 13 days, caused a dramatic elevation in c-fos expression. This effect was significantly attenuated in animals treated chronically with methylphenidate (2 or 10 mg/kg) for the entire 14 days. Our data suggest that repeated methylphenidate treatment, at a clinically relevant dose (2 mg/kg), markedly inhibits immediate-early gene expression in the brain. This is the first demonstration of methylphenidate-induced modification of gene expression in developing rat striatum and may have implications for chronic methylphenidate use in children.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Stimulants / administration & dosage*
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism*
  • Densitometry
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Gene Expression / drug effects*
  • Genes, Immediate-Early
  • Immunohistochemistry
  • Male
  • Methylphenidate / administration & dosage*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Sexual Maturation


  • Central Nervous System Stimulants
  • Proto-Oncogene Proteins c-fos
  • Methylphenidate