Methylphenidate leads to disruptions in rest/wake patterns after discontinuation

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Abstract
Children with attention-deficit/hyperactivity disorder (ADHD) experience more sleep problems than their peers. As stimulant medications, particularly methylphenidate (MPH), are the most common treatment for pediatric ADHD, there has been growing interest in whether such medications contribute to sleep disturbances and the development of sleep disorders later in life. Despite ongoing interest, evidence related to MPH on sleep functioning in children remains mixed. The present study investigated the effects of MPH on 24-hour rest/wake activity patterns and circadian rhythms in adolescent versus adult rats. Male and female Long-Evans rats were administered MPH (1 or 2 mg/kg, i.p.) or control twice daily for 10 days during either adolescence (PD 30–39) or adulthood (PD 80–89). Non-invasive activity monitors, secured to each rat using custom-fitted jackets, were used to assess circadian rhythms and detailed activity patterns over a 24-hour reverse light/dark cycle. Microanalysis of activity patterns were assessed on the last day of MPH treatment, during acute discontinuation, and after 10 days of prolonged discontinuation. Results showed that repeated MPH administration produced dose- and age-specific increases in activity across the light/dark cycle on the last day of treatment. In adults, this was associated with longer and more frequent active episodes during the dark period, and transient increases in fragmented activity during early withdrawal. MPH also impaired rest quality in female rats, reflected by fewer rest episodes and increased fragmentation during the light period. While some of these disruptions persisted immediately after discontinuation, more pronounced impairments in rest quality emerged after 10 days of withdrawal. These findings suggest that while MPH may enhance activity during treatment in an age- and sex-dependent manner, its discontinuation may lead to lasting reductions in sleep quality in both adolescents and adults who are transiently exposed to the psychostimulants.
Funding Information
  • National Institute of General Medical Sciences (T34GM136467)
  • National Institute of General Medical Sciences (R16GM154678)

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