Oral methylphenidate improves spatial learning and memory in pre- and periadolescent rats.

Methylphenidate (MPD) is widely prescribed for attention-deficit/hyperactivity disorder in the United States. Patients, mostly school-age children, are taking the drug orally. To simulate the human condition, the authors used a cracker to administer methylphenidate orally (without the stress of handling) from Postnatal Day (PND) 22 to PND 40 and determined the effects of daily low-dose administration on the learning and performance of a radial arm maze win-shift task with all 8 arms baited. Number of entries to repeat, time to finish 8 entries, and days to reach criterion (at least 7 entries without errors for 4 out of 5 consecutive trials) were evaluated. An improvement during the first 7 days was revealed in both male and female rats treated with 3.0 mg/kg of oral methylphenidate compared with the controls. On PND 40, locomotor activity levels were not significantly different in the 3.0 mg/kg treated group compared with the controls during the initial 5 min or during the full 1 hr of recording. These data suggest that oral administration of low-dose MPD improves spatial learning and memory in both male and female preadolescent rats.