Subchronic methylphenidate administration has no effect on locomotion, emotional behavior, or water maze learning in prepubertal mice

Abstract

Methylphenidate hydrochloride (Ritalin, MPH) is frequently prescribed as a treatment for children with attention deficit hyperactivity disorder (ADHD), yet little research has been conducted to determine its potential long-term neurobehavioral effects. We assessed the effects of subchronic MPH administration (2.5, 5, 10, 20, 40, or 80 mg/kg) on male CD-1 mice treated from 26 to 32 days of age. When tested at 33 days of age in the open field and elevated plus maze, there were no significant differences in spontaneous locomotion, exploration, or fear- and anxiety-related behaviors. Testing from 34 to 37 days of age in a water maze task revealed no significant effects of any dose of MPH on learning in this simple paradigm. While it is difficult to extrapolate directly from these results to clinical effects in humans, our results indicate that preexposure of mice to MPH late in the postnatal developmental period does not appear to alter later behavior. We are currently conducting additional studies to further probe the potential effects of MPH administration during development and to examine various contributing factors including stage of development, duration of MPH administration, complexity of the task used to assess behavioral changes, and type of cognitive process being analyzed (attention, nonspatial working memory, etc.).

Alterations in brain neurotrophic and glial factors following early age chronic methylphenidate and cocaine administration

“…These results are consistent with Zubrycki et al [29], Broderick et al [30] and Damianopoulos and Carey [31], who showed increased locomotion in an open field test following cocaine administration compared to saline-treated rats. McFadyen et al [32], and Ferguson and Cada [33] exhibited similar results to ours, showing no methylphenidate effect on open field performance. On the contrary, Yang et al [34] showed increased locomotion 20 min after methylphenidate administration.…”

Methylphenidate Administration to Juvenile Rats Alters Brain Areas Involved in Cognition, Motivated Behaviors, Appetite, and Stress

“…Some studies show decreases (McFadyen-Leussis et al, 2004), and others show increases (Carrey et al, 2000;McFadyen et al, 2002;Bolanos et al, 2003) in anxiety-like behaviors after MPH administration. In the present study, two tests were performed to assess anxiety levels in the male PND135 rats, which received MPH or saline from PND7-PND35 and then were drug-free for 3 months.…”

Juvenile Methylphenidate Exposure and Factors That Influence Incentive Processing

“…For example, juvenile exposure to MPH produces an aversion to cocaine-associated environments in adulthood [7, 8], whereas exposure during adolescence [9] or adulthood [10] increases self-administration of cocaine. Other studies report no significant behavioral effect [11]. …”