Stimulant abuse remains a social problem. Studies of the reinforcing and subjective effects of stimulants, specifically amphetamine and cocaine, report variations in subjective and reinforcing effects among individuals and within individuals as a function of time-of-day. The variations may be due, in part, to differences in daytime sleepiness-alertness. Daytime sleepiness-alertness can be reliably and validly measured using standard electrophysiological methods and it varies within and among healthy individuals as a function of time-of-day and the prior amount of sleep. To further understand the conditions leading to stimulant use and abuse, this project will explore how sleepiness-alertness influences the reinforcing and subjective effects of methylphenidate in healthy adults without drug abuse histories. Methylphenidate will be studied because it is the most often prescribed stimulant and primarily to a population known to be sleepy due to sleep loss. Thus, the working hypothesis of this project is that one way stimulants, and specifically methylphenidate, may gain reinforcing effects is by enhancing behavioral function and alertness in """"""""sleepy"""""""" people. The project will combine established methods of assessing the reinforcing and subjective effects of drugs with standard sleep laboratory methology and performance testing to document levels of sleepiness and the alerting and behaviorally enhancing effects of methylphenidate. Four experiments exploring the modulating role of sleepiness-alertness for the reinforcing and subjective effects of methylphenidate are proposed for the five year grant period. Over the first two years a parametric analysis will be done of the interaction of time-in-bed (TIB) and its consequent sleepiness-alertness with doses of methylphenidate. During the third year the investigator will determine whether the level of sleepiness-alertness during one's initial experience with methylphenidate is important to its subsequent reinforcing and subjective effects. In year four, rather than exploring state differences in sleepiness-alertness, trait-like differences in sleepiness-alertness will be the study focus. And finally during year five the interaction of behavioral demand placed on subjects and different levels of sleepiness-alertness will be the focus.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Clinical Neuroscience and Biological Psychopathology Review Committee (CNBP)
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Wetherington, Cora Lee
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Henry Ford Health System
Schools of Medicine
United States
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Roehrs, Timothy A; Roth, Thomas (2015) Sleep Disturbance in Substance Use Disorders. Psychiatr Clin North Am 38:793-803
Drake, Christopher L; Roehrs, Timothy; Turner, Lauren et al. (2003) Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance. Neuropsychopharmacology 28:371-8
Roehrs, Timothy; Hollebeek, Emily; Drake, Christopher et al. (2002) Substance use for insomnia in Metropolitan Detroit. J Psychosom Res 53:571-6
Roth, T; Roehrs, T (2001) Sleep-wake variations and drug self-administration. Arch Ital Biol 139:243-52