title: Effect of three caffeine doses on plasma catecholamines and alertness during prolonged wakefulness.
abstract: OBJECTIVE
  Determine the relationship between caffeine, catecholamines, and alertness during prolonged wakefulness.
  
  
  METHODS
  Following 49 h of prolonged wakefulness, each of 50 healthy males (18-32 years) orally ingested either a placebo or one of three doses of caffeine, 2.1 (low), 4.3 (medium), or 8.6 mg kg-1 body weight (high), in a randomized double-blind design. Wakefulness continued for an additional 12 h during which venous blood samples were collected for catecholamine and caffeine analysis [determined using high-performance liquid chromatography (HPLC)]. A sleep latency test, the Stanford sleepiness scale, and a choice reaction time test were administered periodically during the post-dosing period and served as measures of alertness (physiological, subjective, and behavioral, respectively).
  
  
  RESULTS
  Caffeine had no significant effect on noradrenaline, but adrenaline was significantly increased between 1 h and 4 h post-dosing in the high dose group compared with a placebo group. Following caffeine administration, responses to sleep latency, sleepiness scores, and reaction time scores showed dose-related changes that were exhibited by significant correlation coefficients.
  
  
  CONCLUSIONS
  The results indicate that high doses of caffeine have a significant and beneficial effect on alertness during prolonged wakefulness.
authors.affiliation: Department of Neurobiology and Behavior, Division of Neuropsychiatry, Walter Reed Army Institute of Research, Washington, DC 20307-5100, USA. gary.kamimori@na.amedd.army.mil
authors.forename: G H
authors.initials: GH
authors.lastname: Kamimori
authors.forename: D M
authors.initials: DM
authors.lastname: Penetar
authors.forename: D B
authors.initials: DB
authors.lastname: Headley
authors.forename: D R
authors.initials: DR
authors.lastname: Thorne
authors.forename: R
authors.initials: R
authors.lastname: Otterstetter
authors.forename: G
authors.initials: G
authors.lastname: Belenky
mesh_terms: D000293:Adolescent; D000328:Adult; D002110:Caffeine / Q000097:blood / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000097:blood / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004837:Epinephrine / Q000097:blood*; D006801:Humans; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D012892:Sleep Deprivation / Q000097:blood* / Q000523:psychology; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D002110:Caffeine; D009638:Norepinephrine; D004837:Epinephrine