Chronic oral methylphenidate (MP) exposure in rats is associated with numerous developmental and behavioral consequences. The present study investigated the persistence of the effects of chronic oral MP exposure after abstinence from MP use. Male and female rats were exposed to daily orally self-administered water, low dose MP (LD), or high dose (HD) MP for 13 weeks, followed by a 4-week abstinence period. Fluid, food consumption and bodyweights were monitored and animals were tested for locomotor activity, anxiety- and depressive-like symptoms, learning and memory, and social behavior during both the treatment and abstinence phases of the experiment. During treatment, MP attenuated bodyweight regardless of sex, but increased food and fluid consumption in females and males by 20.7% and 30.1%, respectively. MP also increased locomotor activity in both males and females observed as increased distance travelled in an open field. (59.1% and 95.9%, respectively) and increased locomotor activity in the home cage over a 24-hour circadian cycle (45.5% and 63.0%). Additionally, MP exerted an anxiolytic effect observed as increased time spent in the open arms of an elevated plus maze (31.1% in HD males, 59.2% in HD females), and an increased latency to immobility in a forced swim test (330% in HD males, 418% in HD females). The effects of MP (bodyweight, consumption, locomotion, anxiolytic, and anti-depressive) were, almost without exception, eliminated during the abstinence period. MP had no impact on learning and memory performance as measured by a T-maze, or social behavior during treatment. These findings suggest that the behavioral consequences of chronic oral MP treatment in our preclinical model are reversible in rats following an abstinence period from use of the drug.

Methylphenidate (MP) is a commonly prescribed psychostimulant for Attention Deficit Hyperactivity Disorder (ADHD). We recently reported behavioral and developmental effects of chronic MP use in healthy rats. The current study investigated how interrupting chronic MP treatment with weekend abstinence altered the behavioral and physiological consequences of chronic MP treatment, and if prolonged abstinence would reverse the observed effects. Male Sprague Dawley rats were assigned to one of three treatment groups: water (W); low dose (LD) MP; and high dose (HD) MP. For 13 weeks, rats had access to drink from a bottle containing 4 mg/kg MP (LD), 30 mg/kg MP (HD) or water (W) for 1 hour, and 10 mg/kg MP (LD), 60 mg/kg MP (HD) or water (W) for the next 7 hours, each week day. During weekends, all animals received only water as well as throughout the 5-week-long abstinence phase, which immediately followed the treatment phase. Throughout the treatment phase, regardless of weekend abstinence, chronic MP resulted in significant decreased food and fluid intake and body weight. Also, HD MP exposure resulted in the following behavioral effects: increased open field and circadian locomotor activity; increased latency to immobility and decreased time spent immobile in the forced swim test; increased center activity in the open field and percent of time spent in an open arm of the elevated-plus-maze; and increased social affiliation and memory in the Crawley’s three chamber sociability test. During the prolonged (5-week) abstinence phase, all these effects were reversed while HD treated rats increased their fluid intake. These results indicated that intermittent brief abstinence periods (weekend’s off-treatment) produced the same behavioral and developmental effects as those previously reported with chronic (7 days/week) MP treatment, but were reversible following a prolonged abstinence period (5 weeks).