Effect of three caffeine doses on plasma catecholamines and alertness during prolonged wakefulness.

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. CONCLUSION: The results indicate that high doses of caffeine have a significant and beneficial effect on alertness during prolonged wakefulness.

Decoupling motor memory strategies: effects of sleep deprivation and amphetamine.

The purpose of this study was to examine motor memory strategies using sleep deprivation as a probe. Eighteen healthy men participated in a three-day study in which they underwent repeated testing on a kinesthetic arm position replication task. On the morning of Day 3, after approximately 48 hr sleep deprivation, they ingested either 20 mg d-amphetamine or placebo. Results showed that throughout Day 3 performance remained relatively unimpaired at medial positions for both groups. For positions shifted 25 degrees laterally, accuracy was also relatively unimpaired for the amphetamine group but was compromised for the placebo group. It was concluded that sleep deprivation-induced decrements in positioning ability were due to disruption of kinesthetic memory, a narrowing of attention, or both. Kinesthetic feedback, and encoding and retrieval processes of the spatial reference system were preserved.

Effects of catecholamine depletion on alertness and mood in rested and sleep deprived normal volunteers.

Alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, was used to evaluate the physiologic role of central nervous system catecholamines in modulating alertness and mood. Forty healthy males were randomized to one of four conditions: AMPT in a rested condition; AMPT plus 40.5 hours of total sleep deprivation; placebo plus sleep deprivation; or placebo in a rested condition. Repeated measures of alertness and mood revealed that treatment with AMPT or sleep deprivation increased sleepiness, and combined treatment produced greater sleepiness than either treatment alone. In contrast, although combined treatment with AMPT and sleep deprivation led to large increases in negative mood, neither treatment alone produced consistent mood changes. These findings are consistent with the view that sleep deprivation is associated with decreased functional catecholamine neurotransmission. Furthermore, mood effects following sleep deprivation plus AMPT suggest that catecholamines may be involved in mood changes during sleep deprivation.

Parsing attentional components during a simple reaction time task using sleep deprivation and amphetamine intervention.

To examine the independent contributions of the attentional components of arousal and activation in performance, sleep deprivation was used as the attentional manipulation in a reaction time (RT) task. The subjects were 18 men who underwent 63 hr. of sleep deprivation during which time they periodically performed a simple auditory RT task with manipulations of temporal uncertainty and intensity. After 48 hr. sleep deprivation, subjects ingested either 20 mg d-amphetamine or placebo, then continued testing throughout Day 3. During sleep deprivation, performance was more impaired on trials associated with low temporal uncertainty (arousal) and high preparation (activation) than on trials associated with high temporal uncertainty and low preparation. Analysis indicated that sleep deprivation perturbed activation, leaving arousal relatively unimpaired and that amphetamine had a restorative effect on the sleep deprivation-impaired activation system. The stimulus of high intensity was disruptive on Day 1 but facilitative on Day 3, a result which was interpreted as an initial inhibition, then disinhibition of arousal. Results were interpreted to indicate that, in some instances, alterations in the less specific arousal and activation systems may underlie impairment or changes in the more specific information processing and motor output stages.

Sleep deprivation and impaired cognition. Possible role of brain catecholamines.

To assess the role of brain catecholamines in cognitive decline associated with sleep deprivation, 40 healthy male volunteers were randomized to conditions of total sleep deprivation or 40.5 h of rest. Within each sleep condition, subjects were further randomized to treatment with a 2-day regimen of placebo or alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor. Cognitive performance was measured repeatedly over time using a computerized performance assessment battery. Treatment with AMPT or treatment with sleep deprivation increased sleepiness without producing marked or consistent deterioration in performance. By contrast, subjects who received both treatments reported greater sleepiness than those receiving either treatment alone, and developed severe cognitive impairment on a variety of tasks. These findings, along with previous evidence that catecholamine-enhancing drugs improve performance in sleep-deprived individuals, support the view that decline in cognitive performance during sleep deprivation may be mediated by brain catecholamines.

Circadian variation in human performance evaluated by the Walter Reed performance assessment battery.

As part of a two clock-time (0830 versus 2030) evaluation of administration-time dependent effects of dexedrine (5 mg) and triazolam (0.25 mg) on human cognitive performance, placebo (control) studies were conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized crossover design. Testing was conducted hourly during a series of sleepless 13-hr spans commencing in the morning or evening, using the Walter Reed computer controlled and scored multi-task cognitive performance assessment battery. For the placebo condition, Single and Group Cosinor analyses documented circadian rhythms in performance for most tasks (reaction time, logical reasoning, serial add/subtract and spatial orientation) both for individuals and the group. Overall, performance was worse overnight, when sleepiness was greatest, and best between 1830 and 2030. It was most variable around 0600-0700. The day-night variation in performance over all cognitive tests amounted to 21% of the 24-hr mean.

Perceptual distortions and hallucinations reported during the course of sleep deprivation.

Subjects worked 30 to 45 min. of each hour for either 48 (n = 2) or 72 hr. (n = 8) without sleep. The frequency of reported visual task-related perceptual distortions and hallucinations showed both a linear increasing component and a strong circadian component. Perceptual distortions were most frequent in the late night-early morning hours (0400) and least frequent in the late afternoon-early evening hours (1600-2000).

The Walter Reed performance assessment battery.

This paper describes technical details of a computerized psychological test battery designed for examining the effects of various state-variables on a representative sample of normal psychomotor, perceptual and cognitive tasks. The duration, number and type of tasks can be customized to different experimental needs, and then administered and analyzed automatically, at intervals as short as one hour. The battery can be run on either the Apple-II family of computers or on machines compatible with the IBM-PC.

Effects of 72 hour sleep deprivation on urinary cortisol and indices of metabolism.

Cortisol, urea, glucose, electrolytes, and other compounds were measured in five consecutive 24 h urine collections during a 72 h sleep deprivation study in six young men. Urine was collected during a 24 h predeprivation day, 3 days of sleep deprivation, and a recovery day. Whereas urinary cortisol decreased only slightly, marked changes in other urinary constituents were observed. During sleep deprivation, urinary urea rose markedly, glucose decreased, and urinary electrolytes decreased. These data indicate that sleep deprivation under ad lib food and water conditions can cause disturbances in normal metabolism.

Sulfated glycoproteins, glycolipids, and glycosaminoglycans from synaptic plasma and myelin membranes: isolation and characterization of sulfated glycopeptides.

In this report we provide biochemical evidence that a highly purified synaptic plasma membrane fraction derived from rat brain, after intraventricular injection of 35S-labeled sodium sulfate, is enriched in a number of large sulfated glycoproteins compared with a purified myelin fraction studied concurrently. A fraction of the detergent-solubilized sulfated glycoprotein bound specifically to concanavalin A-Sepharose. In addition, we have identified the 35S-labeled lipid-soluble material in these membrane fractions as cerebroside sulfate. The sulfated protein in the lipid-extracted membranes was shown to consist predominantly of a class of glycoproteins containing sulfate in ester linkage to oligosaccharide chains, which are differentiated structurally from the sulfated glycosaminoglycans of brain. These two classes of sulfated macromolecules were distinguished from one another by several chemical and physical parameters. We present the chemical characterization of the sulfated glycopeptides derived from synaptic plasma and myelin membranes by extensive proteolytic digestion after quantitative removal of cerebroside sulfate. Membrane-associated glycosaminoglycans, either specifically or adventitously associated with these neuronal membranes, were quantitatively precipitated and identified.