Object memory impairment at post-drug Day 15 but not at Day 1 after a regimen of repeated treatment with oral methylphenidate

•Sub-chronic methylphenidate impaired object memory when rats were tested post-drug.•Oral methylphenidate (5.0mg/kg) was administered twice daily on 21 occasions.•Impairment of memory was only evident after a 14-day drug washout period. Methylphenidate (MPH) is a dopamine and norepinephrine reuptake inhibitor that is widely used for the treatment of attention-deficit/hyperactivity disorder in children and adults. Its similarity to other psychostimulants suggests that, at certain doses, the drug may generate lasting neuroadaptations that can be detrimental to the recipient. Some investigators have found that, in rats, the residual effects of the drug (i.e., following a 10–14 day washout period) can interfere with memory for objects when the retention interval is 3h or more. The present experiment replicated this result and demonstrated the critical importance of the washout period. Long-Evans male rats treated with MPH (5.0mg/kg po b.i.d.) on 21 days (during a post-natal period ranging from Day 29 to Day 57) and then twice-assessed for their performance in an object recognition task were able to recognize a familiar object on Day 1 after the last dose of the drug had been administered, behaving the same as the untreated control group. However, on Day 15 post-drug, the same MPH group failed to distinguish between a familiar and a novel object, exploring both nearly equally, while the control group continued to investigate the novel object to a greater extent than the familiar one. This suggests that, if a test for object recognition is conducted too early after the MPH treatment period ceases, a memory impairment may not be detected. In general, this finding has implications for studies of other behavioral or neurophysiological consequences of MPH that may appear following a drug-free withdrawal period.