Dose-related immunohistochemical and ultrastructural changes after oral methylphenidate administration in cerebrum and cerebellum of the rat.
Methylphenidate is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder of children and young adults. Our aim is to investigate dose-dependent dopamine-2 receptor and glial fibrillary acidic protein expression and ultrastructural changes of the rat brain, to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. 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 methylphenidate dissolved in saline solution for 5 days per week during 3 months. At the end of the third month, tissues were removed and sections were collected for immunohistochemical and ultrastructural studies. We believe that methylphenidate causes dose-related activation of the dopaminergic system in several brain regions especially in ventral tegmental area and also causing neuronal degeneration and capillary wall structural changes such as basal membrane thickness and augmentation of the pinostatic vesicle in the endothelial cells. Also, increased dose of Ritalin is inducing astrocytes hypertrophy especially astrogliosis in pia-glial membrane and this is the result of the degenerative changes in prefrontal cortex region due to high dose methylphenidate administration. The dose-related accumulation of the astrocytes in capillary wall might well be a consequence of the need for nutrition of the neuronal tissue, due to transport mechanism deficiency related to neuronal and vascular degeneration. Thus, we believe that the therapeutic dose of methylphenidate must be kept in minimum level to prevent ultrastructural changes.
Bahcelioglu
Meltem
M
Department of Anatomy, Faculty of Medicine, University of Gazi, Ankara, Turkey. meltemb@gazi.edu.tr
Gozil
Rabet
R
Take
Gulnur
G
Elmas
Cigdem
C
Oktem
Hale
H
Kadioglu
Dural
D
Calguner
Engin
E
Erdogan
Deniz
D
Sargon
Mustafa F
MF
Yazici
A Canan
AC
Tas
Murat
M
Bardakci
Yesim
Y
Senol
Selahattin
S
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000633:toxicity*; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D054022:Cerebrum / Q000187:drug effects* / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008774:Methylphenidate / Q000008:administration & dosage / Q000633:toxicity*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D010873:Pinocytosis / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000473:pathology
D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D004298:Dopamine