Immunohistochemical and Ultrastructural Changes Related To Methylphenidate In Rat Pituitary and Pineal Glands

Objective: The presence of a dopaminergic function in pituitary and pineal glands is well known. Methylphenidate (MPH), a widely prescribed psychostimulant for attention deficit/hyperactivity disorder, is an indirect dopamine agonist which could have the capacity of influencing the hypothalamo-neurohypophysial system with the pineal gland. Our aim is to investigate dose-dependent immunohistochemical dopamine 2 expression, possible cell apoptosis and ultrastructural changes of the rat pituitary and pineal gland tissue, to demonstrate possible toxicity of the chronic extended use of the MPH.Material and Methods: In this study, 27 female prepubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg), were treated orally with MPH dissolved in saline solution for 5 days per week during three months. At the end of the third month, after perfusion fixation, pituitary and pineal glands were removed and sections were collected for immunohistochemical, TUNEL assay and ultrastructural studies.Results: We observed that methylphenidate induced dose-related ultrastructural changes in pituitary and pineal glands.Conclusion: High dose administration of this drug could influence the functions of these glands. Thus, we suggest that the therapeutic dose of methylphenidate must be kept in minimum level.