Protective effects of forced exercise against methylphenidate‑induced anxiety, depression and cognition impairment in rat

Methylphenidate (MPH), a neural stimulant, can cause damages to brain; the chronic neurochemical and behavioral effects of MPH remain unclear. Exercise lowers stress and anxiety and can act as non‑pharmacologic neuroprotective agent. In this study protective effects of exercise in MPH‑induced anxiety, depression and cognition impairment were investigated.

Seventy adult male rats were divided randomly into five groups. Group 1 served as negative control, received normal saline (0.2 ml/rat) for 21 days, group 2 and 3 (as positive controls) received MPH (10 and 20 mg/kg) for 21 days. Groups 4 and 5 concurrently were treated with MPH (10 and 20 mg/kg) and forced exercise for 21 days. On day 21, Elevated Plus Maze (EPM), Open Field Test (OFT), Forced Swim Test (FST) and Tail Suspension Test (TST) were used to investigate the level of anxiety and depression in animals. In addition between 17th and 21th days, Morris Water Maze (MWM) was applied to evaluate the effect of MPH on spatial learning and memory.

MPH‑treated animals indicated a reflective depression and anxiety in a dose‑dependent manner in FST, EPM and TST which were significantly different from the control group and also can significantly attenuate the motor activity and anxiety in OFT. Forced exercise by treadmill can attenuate MPH‑induced anxiety, depression and motor activity alteration in OFT. MPH also can disturb learning and memory in MWM and forced exercise can neutralize this effect of MPH.

We conclude that forced exercise can be protective in brain against MPH‑induced anxiety, depression and cognition alteration.