Dose-dependent immunohistochemical and ultrastructural changes after oral methylphenidate administration in rat heart tissue

Anat Histol Embryol. 2008 Aug;37(4):303-8. doi: 10.1111/j.1439-0264.2008.00845.x. Epub 2008 Feb 13.


Methylphenidate, more commonly known as Ritalin, is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder, one of the most common behavioural disorders of children and young adults. Our aims were to investigate dose-dependent immunohistochemical D2 expression and ultrastructural changes of the rat heart tissue, and to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female pre-pubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) and their control groups, were used. They were treated orally with methylphenidate dissolved in saline solution for 5 days/week during 3 months. At the end of the third month, after perfusion fixation, left ventricle of cardiac tissue was removed. Paraffin, semi-thin and thin sections were collected and immunohistochemical, terminal deoxynucleotidyl transferase-mediated Dig-dUTP nick end labelling assay and ultrastructural studies were performed. In conclusion, we believe that Ritalin is dose-related affecting dopaminergic system to increase heart rhythm and contraction. Thus, this drug may cause degenerative ultrastructural changes in mitochondrial path.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Female
  • Heart / anatomy & histology*
  • Heart / drug effects*
  • Immunohistochemistry / veterinary
  • Methylphenidate / pharmacology*
  • Myocardium / ultrastructure*
  • Random Allocation
  • Rats
  • Rats, Wistar


  • Methylphenidate