Impact of preadolescent psychostimulants on neurophysiology and sleep/wake disturbances

PROJECT SUMMARY Children with attention-deficit/hyperactivity disorder (ADHD), whether taking stimulant medications or not, experience more sleep problems than their peers. These nighttime sleep problems often lead to daytime sleepiness, which is likely to exacerbate some of the negative behavior effects commonly associated with ADHD.

Since the most common treatment for pediatric ADHD is psychostimulant medication, methylphenidate (MPH), there has been a long-standing interest in whether this type of medication results in exacerbated sleep disturbances and the further development of sleeping disorders later in adulthood. Despite ongoing interest in

the association between stimulant use and sleep in children, there is a lack of evidence regarding the causal effects of MPH on the sleep functioning of children with ADHD. The goal of the proposed grant is to break down the complex relationship that early psychostimulant exposure and ADHD can have on sleep neurophysiology

and whether this effect is unique to developmental exposure and persists into adulthood. The first aim of this grant will study the effects of MPH on sleep architecture and neurophysiological activity (sleep EEG and waking ERPs) in spontaneously hypertensive rats (SHR), a well-established and validated model of ADHD, compared

to the inbred Wistar-Kyoto rat control strain. EEG can be used in rodents to provide a translational model of not only sleep architecture and neuroactivity, but ERPs can be used as a predicting biomarker for neurological disorders. Study 1A will investigate effects of MPH on sleep patterns and EEG/ERP activity in preadolescent

ADHD rat model of both sexes. Study 1B will determine whether these effects of preadolescent methylphenidate on sleep patterns and EEG activity will persist into adulthood. The second aim will determine if preadolescent MPH alters circadian rhythm and light/dark activity throughout the lifespan in ADHD rat models of both sexes.

Study 2A investigates how circadian rhythms and light/dark activity patterns can change across the lifespan in the SHR compared to the Wistar-Kyoto control strain. This study will also determine whether behavioral measures common in ADHD (e.g. inattention, hyperactivity, disinhibition) may correlate with sleep quality and

quantity throughout the lifespan. Study 2B will investigate how preadolescent psychostimulant medication in SHR and control strain rats can alter these circadian rhythm, light/dark activity, and behavioral measures throughout development and into adulthood.