Chronic administration of methylphenidate did not affect memory and GDNF levels but increase astrogliosis in adult male rat’s hippocampus

•MPH blocks dopamine and norepinephrine transporters, resulting in inhibition of the reuptake of these monoamines.•Attention deficit hyperactivity disorder (ADHD) is a kind of neuropsychiatric disorder prevalent nowadays commonly among school-aged children as well as adolescents. ADHD is the most common developmental disorder affecting approximately three to seven percent of school-aged children and 2.5 percent of adults worldwide. The drug of choice for the pharmacotherapy of ADHD is Methylphenidate (MPH). However, there is growing concerns about side effects resulting from its potential interference with brain anatomical and behavioral development. This article focuses on the adverse effects of MPH on the rat’s hippocampus. The animals received an oral dose of 5 mg/kg MPH or normal saline, as the vehicle, on a daily basis for 30 days. Y-maze test, passive avoidance, Barnes maze and field potential recording were conducted. Western blot for detecting the neurotrophic factor of GDNF and immunohistochemistry of astrogliosis were performed. Our results revealed that MPH treatment suppressed the willingness of rats to explore new environments. Also, it had no effect on improving long-term potentiation, long-term memory and spatial memory in the MPH group as opposed to the control group. There was also a significant increase of astrogliosis in the treated rats’ hippocampi. On the other hand, there was not a significant relationship between MPH administration and the decrement of the GDNF level. We encourage the need to conduct more research on the adverse effects of MPH on the brain.