Methylphenidate (MPH) remains an important therapy for Attention-Deficit Hyperactivity Disorder but aspects of its pharmacology remain unclear. In the present study, we used a regimen of MPH (8 mg/kg daily X 14 days) in C57BL/6J mice to determine whether establishing locomotor sensitization to MPH influenced the acquisition and the dose-response function of MPH in a classic drug discrimination procedure. MPH-sensitized mice (SENS group) demonstrated enhanced locomotor activity to the 8 mg/kg exposure dose as well as a 2mg/kg dose prior to discrimination training. However, the SENS mice did not acquire discrimination of either a low dose (2mg/kg) or a higher dose (4mg/kg) of MPH any more rapidly than the CTRL mice. Further, during generalization testing, the dose-response functions for the SENS and CTRL mice were identical. Therefore, we did not find that prior exposure to MPH, which produced a sensitized locomotor response, facilitated MPH discrimination.
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