Methamphetamine attenuates disruptions in performance and mood during simulated night-shift work

Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Psychopharmacology (Impact Factor: 3.88). 09/2003; 169(1):42-51. DOI: 10.1007/s00213-003-1464-4
Source: PubMed


Increased sleepiness while working and sleep disruptions are common complaints among shift workers. Consequently, shift workers may be more susceptible to diminished performance and work-related accidents.
To examine the effects of the central nervous system stimulant methamphetamine on psychomotor task performance, subjective effects, and food intake during shift work under laboratory conditions.
Seven participants completed this 23-day, within-participant design, residential laboratory study. They received a single oral methamphetamine dose (0, 5, 10 mg) 1 h after waking for three consecutive days under two shift conditions: (1) during the day shift, participants performed computerized psychomotor tasks from 0830 hours to 1730 hours and went to bed at 2400 hours and (2) during the night shift, participants performed tasks from 0030 hours to 0930 hours and went to bed at 1600 hours. Shifts alternated three times during the study; shift conditions were separated by an "off" day during which participants were not on a schedule and data were not collected.
When participants received placebo, psychomotor task performance and subjective effects were disrupted during the night shift, relative to the day shift. Changing shift conditions did not alter food intake significantly. Methamphetamine reversed performance and subjective-effects disruptions, and decreased food intake during the night shift.
These data indicate that shift changes produce performance impairments and mood alterations, and that a single low to moderate dose of methamphetamine attenuates many shift change-related disruptions in performance and mood.

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    • "In contrast, unpublished data from this experiment reveal that when the same participants received 5 mg MA at 0915, their ratings of " good drug effects " were indistinguishable from ratings for placebo [Fig. S1.a (data) and b (study design)], (Supplementary material; Hart et al., 2003). While this experiment was not designed to examine the influence of time of day, the results do raise a question about how such an effect might influence drug self-administration: a question optimally addressed in studies of laboratory animals. "
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    ABSTRACT: The circadian timing system influences a vast array of behavioral responses. Substantial evidence indicates a role for the circadian system in regulating reward processing. Here we explore time of day effects on drug anticipation, locomotor activity, and voluntary methamphetamine (MA) and food intake in animals with ad libitum food access. We compared responses to drug versus a palatable treat during their normal sleep times in early day (zeitgeber time (ZT) 0400) or late day (ZT 1000). In the first study, using a between-subjects design, mice were given daily 1-hr access to either peanut butter (PB-Alone) or to a low or high concentration of MA mixed in PB (MA+PB). In study 2, we repeated the experiment using a within-subjects design in which mice could choose between PB-Alone and MA+PB at either ZT 0400 or 1000. In study 3, the effects of MA-alone were investigated by evaluating anticipatory activity preceding exposure to nebulized MA at ZT 0400 vs. ZT 1000. Time of day effects were observed for both drug and palatable treat, such that in the between groups design, animals showed greater intake, anticipatory activity, and post-ingestional activity in the early day. Furthermore, there were differences among mice in the amount of MA ingested but individuals were self-consistent in their daily intake. The results for the within-subjects experiment also revealed robust individual differences in preference for MA+PB or PB-Alone. Interestingly, time of day effects on intake were observed only for the preferred substance. Anticipatory activity preceding administration of MA by nebulization was also greater at ZT 0400 than ZT 1000. Finally, pharmacokinetic response to MA administered intraperitoneally did not vary as a function of time of administration. The results indicate that time of day is an important variable mediating the voluntary intake and behavioral effects of reinforcers.
    Pharmacology Biochemistry and Behavior 05/2013; 110. DOI:10.1016/j.pbb.2013.05.011 · 2.78 Impact Factor
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    • "These elevated scores raise the concern that sleep deficiencies can precipitate Meth use as a way to reduce daytime sleepiness and to increase alertness and attention. In fact, related studies reported that Meth administration is associated with reduced self-reported fatigue and daytime sleepiness (Shappell et al. 1996) and improved performance on measures of information-processing speed (Hart et al. 2003). "
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    ABSTRACT: The purpose of this study was to evaluate the effects of acute, oral modafinil (200 mg) exposure on daytime sleepiness in methamphetamine (Meth)-dependent individuals. Eighteen Meth-dependent subjects were enrolled in a 7-d inpatient study and were administered placebo or modafinil on day 6 and the counter-condition on day 7 (randomized) of the protocol. Subjects completed several subjective daily assessments (such as the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index, Beck Depression Inventory and visual analogue scale) throughout the protocol as well as objective assessments on days 5-7, when the Multiple Sleep Latency Test was performed. The results of the current study suggest that short-term abstinence from Meth is associated with increased daytime sleepiness and that a single dose of 200 mg modafinil reduces daytime somnolence in this population. In addition, a positive correlation was found between subjective reporting of the likelihood of taking a nap and craving and desire for Meth, as well as the likelihood of using Meth and whether Meth would make the participant feel better. The results of this study should be considered when investigating candidate medications for Meth-dependence, especially in those individuals who attribute their Meth use to overcoming deficits resulting from sleep abnormalities.
    The International Journal of Neuropsychopharmacology 01/2012; 15(9):1241-9. DOI:10.1017/S1461145711001805 · 4.01 Impact Factor
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    • "Intermittent and daily access to methamphetamine selfadministration was performed to mimic the intermittently low and continued high levels of methamphetamine during recreational use in humans that may distinctly affect memory and cognitive function. With regard to psychomotor/cognitive performance in humans, there is general consensus about enhanced cognitive performance with acute (recreational) methamphetamines in methamphetamine-exposed individuals (Johnson et al, 2000, 2005; Hart et al, 2003; Silber et al, 2006) and deficits in cognitive performance in methamphetamine addicts (Scott et al, 2007; Parrott et al, 2011). The current preclinical findings of enhanced spatial memory in the Y-maze and learning in the T-maze by I-ShA rats and impaired performance in LgA rats, therefore, generally agree with the clinical results (Rogers et al, 2008; Reichel et al, 2011). "
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    ABSTRACT: Methamphetamine affects the hippocampus, a brain region crucial for learning and memory, as well as relapse to drug seeking. Rats self-administered methamphetamine for 1 h twice weekly (intermittent-short-I-ShA), 1 h daily (limited-short-ShA), or 6 h daily (extended-long-LgA) for 22 sessions. After 22 sessions, rats from each access group were withdrawn from self-administration and underwent spatial memory (Y-maze) and working memory (T-maze) tests followed by extinction and reinstatement to methamphetamine seeking or received one intraperitoneal injection of 5-bromo-2'-deoxyuridine (BrdU) to label progenitors in the hippocampal subgranular zone (SGZ) during the synthesis phase. Two-hour-old and 28-day-old surviving BrdU-immunoreactive cells were quantified. I-ShA rats performed better on the Y-maze and had a greater number of 2-h-old SGZ BrdU cells than nondrug controls. LgA rats, but not ShA rats, performed worse on the Y- and T-maze and had a fewer number of 2-h-old SGZ BrdU cells than nondrug and I-ShA rats, suggesting that new hippocampal progenitors, decreased by methamphetamine, were correlated with impairment in the acquisition of new spatial cues. Analyses of addiction-related behaviors after withdrawal and extinction training revealed methamphetamine-primed reinstatement of methamphetamine-seeking behavior in all three groups (I-ShA, ShA, and LgA), and this effect was enhanced in LgA rats compared with I-ShA and ShA rats. Protracted withdrawal from self-administration enhanced the survival of SGZ BrdU cells, and methamphetamine seeking during protracted withdrawal enhanced Fos expression in the dentate gyrus and medial prefrontal cortex in LgA rats to a greater extent than in ShA and I-ShA rats. These results indicate that changes in the levels of the proliferation and survival of hippocampal neural progenitors and neuronal activation of hippocampal granule cells predict the effects of methamphetamine self-administration (limited vs extended access) on cognitive performance and relapse to drug seeking and may contribute to the impairments that perpetuate the addiction cycle.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2011; 37(5):1275-87. DOI:10.1038/npp.2011.315 · 7.05 Impact Factor
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