Methylphenidate treated at the test cage--dose-dependent sensitization or tolerance depend on the behavioral assay...

Methylphenidate is the drug most often used to treat attention deficit/hyperactivity disorder (ADHD), a common behavioral disorder of children and young adults. The objectives of this study are (1) to use two different experimental assays of measuring animal activity--the wheel-running activity and the computerized open field--to establish which is more sensitive to acute and repetitive methylphenidate (MPD) administration and (2) to determine whether repetitive MPD treatment elicits adverse effects such as tolerance and behavioral sensitization. The dose-response protocol of MPD (0.6, 2.5, and 10.0 mg/kg) administration was performed in three groups of animals, with an additional saline control group as follows: single saline injection as the control/baseline followed by 6 consecutive days of MPD injections (0.6, 2.5, or 10.0 mg/kg MPD), 3 days of washout, and a day of MPD rechallenge. In general, the two different activity assays showed similar observations for the acute effect of MPD by eliciting increases in activity in a dose-dependent manner. The groups receiving repetitive 0.6 and 2.5 mg/kg MPD tested in the open-field assay exhibited further increase in activity that can be interpreted as behavioral sensitization, whereas the groups receiving 10 mg/kg MPD exhibited a reduction in activity, suggesting that tolerance was developed to the drug. All the groups (0.6, 2.5, and 10.0 mg/kg MPD) tested following repetitive MPD in the wheel-running assay exhibited a further increase in their activity, for example, all the groups exhibited behavioral sensitization. These different observations were interpreted as potentially measuring different kinds of locomotor activity.