Possible Involvement of Glutamatergic, Adrenergic and Dopaminergic System in Methylphenidate - induced Motor Activity and Mood-related Alterations in Rats

Background and Objective: Methylphenidate (MPH), as a central nervous system stimulant, is often used to manage hyperactive disorders. The literature is scarce regarding the behavioral consequences of chronic MPH treatment and the role of involved receptors. Thus, in the current study involved receptors in MPH induced-anxiety, depression and motor activity disorders were evaluated. Materials and Methods: Seventy rats were randomly distributed to seven groups (n = 10, per group); they were treated with normal saline, Domoic acid (DOM) (as AMPA/kainite receptor agonist), Bicuculline (BIC) (as GABAA receptor antagonist), Ketamine (KET) (as NMDA receptor antagonist ), Yohimbine (YOH) (as Alpha-2 adrenergic receptor antagonist), or Haloperidole (HAL) (as D2 dopamine receptor antagonist), simultaneously with MPH (10 mg/kg). On days 11, 17 and 24, some standard behavior tests including Elevated Plus Maze (EPM), Forced Swim Test (FST) and Open Field Test (OFT) were used to investigate anxiety, depression and motor activity disturbances, respectively. Results: Our study indicated that pretreatment of rats with KET, HAL and YOH abolished MPH induced - mood and motor activity disturbances.  Conclusion: MPH by interacting with Dopaminergic, NMDA and ɑ2-adrenergic receptors induces anxiety, depression and motor activity disorders.