Methylphenidate modifies the motion of the circadian clock

People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.Circadian clocks in health and diseas

NEURAL ACTIVITY IN THE SUPRACHIASMATIC CIRCADIAN CLOCK OF NOCTURNAL MICE ANTICIPATING A DAYTIME MEAL

Circadian clocks in health and diseas

Managerial Style and Firm Value

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74402/1/1540-6229.00741.pd

Postprandial metabolic responses to mixed versus liquid meal tests in healthy men and men with type 2 diabetes

AbstractAimsCompare metabolic responses after mixed versus liquid meals of similar caloric/nutritional content in healthy and type 2 diabetes (T2D) subjects.MethodsTen healthy men and 10 men with T2D received mixed and liquid meals after an overnight fast. Classical (insulinogenic index; insulin/glucose areas under curves, AUCinsulin/AUCglucose) and model-based (beta-cell glucose sensitivity; rate sensitivity; potentiation factor ratio, PFR) beta-cell function estimates were calculated. Between-meal differences in glucose, insulin, C-peptide, triglyceride (TG), beta-cell function and oral glucose insulin sensitivity (OGIS) and between-meal correlations for beta-cell function and OGIS were evaluated.ResultsAmong healthy subjects, beta-cell function and OGIS were similar between meals. C-peptide (p=0.03), insulin (p=0.002), AUCinsulin/AUCglucose (p=0.004) and insulin secretion (p=0.04) were higher after the liquid meal. Among T2D subjects, glucose, insulin, C-peptide, beta-cell function, and OGIS were similar. PFR was higher (p=0.004) and TG increased more slowly (p=0.002) after the liquid meal. OGIS and beta-cell function were correlated during both meals in both groups (r=0.66–0.98), except incremental AUCinsulin/AUCglucose, rate sensitivity, and, in healthy subjects, PFR.ConclusionsMetabolic responses after mixed or liquid meals of similar content were highly correlated in T2D and healthy subjects. In T2D, the liquid meal produced beta-cell function estimates generally similar to the mixed meal