Difficulty initiating/maintaining sleep afflicts up to 30% of the population, yet the neurochemical processes associated with sleep and sleep disturbances have not been clearly identified. A better understanding of EEG slow-wave activity and its role in recovery from sleep loss could be invaluable in elucidating the homeostatic sleep mechanism and shedding light on how to treat disturbed sleep. Further, sleep disturbances contribute to relapse to drug use and such efforts might help address this serious public health problem. The purpose of the study is to identify neurochemical markers of sleep mechanism in an intact and an impaired system, by evaluating changes in brain chemistry produced by disrupted sleep. In response to RFA-HL-01-009, """"""""Interrelationship between sleep and heart, lung, and blood diseases"""""""" we propose two experiments. In the first, polysomnography (PSG) and phosphorous magnetic resonance spectroscopic imaging (31P MRSI) will be collected at baseline, after sleep deprivation, and after recovery sleep in controls and in methadone-maintained subjects. Measures will be repeated at 1 and 3 months to determine if the effects persist. In the second experiment, PSG and 31P MRSI data will be collected from unmedicated cocaine-dependent and opiate-dependent subjects during acute withdrawal and at 1 and 3 months post withdrawal. As the abstinence profile for sleep disturbance differs in these groups (hypersomnia vs insomnia, respectively) this experiment will help delineate the conditions under which altered brain bioenergenics exist. 31P MRSI can be used to measure global and focal changes in high energy phosphate alpha-,gamma-,beta-NTP (ATP). Our pilot data showed significant increases in beta-NTP and decreases in phospholipid catabolite production after recovery following sleep deprivation in control subjects. 31P MRS changes have been observed in chronic opiate-dependent individuals at baseline, but have not been evaluated during sleep. Chronic sleep disturbances have been reported in opiate abusers and methadone-maintained patients and the homeostatic sleep mechanisms may be impaired in chronic opiate abuse. We hypothesize that methadone-maintained subjects will have decreased beta-NTP and will exhibit smaller slow wave sleep rebound and a more modest or no increase in beta-NTP after recovery. Further, the neurochemical response to sleep deprivation in these subjects will approach that of controls over time b-NTP will increase during cocaine withdrawal and decrease during opiate withdrawal, reflecting their differential effects on sleep during this time. Collectively, these studies may identify neurochemical markers for the recovery function of sleep, thus enhancing our understanding pf basic sleep mechanisms and potentially leading to new and improved treatments for sleep disturbances in both the substance-abusing and general population.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA016542-04
Application #
7118075
Study Section
Special Emphasis Panel (ZHL1-CSR-P (S1))
Program Officer
Gordon, Harold
Project Start
2003-09-15
Project End
2008-02-29
Budget Start
2006-06-01
Budget End
2008-02-29
Support Year
4
Fiscal Year
2006
Total Cost
$365,781
Indirect Cost
Name
Mc Lean Hospital (Belmont, MA)
Department
Type
DUNS #
046514535
City
Belmont
State
MA
Country
United States
Zip Code
02478
Plante, David T; Trksak, George H; Jensen, J Eric et al. (2014) Gray matter-specific changes in brain bioenergetics after acute sleep deprivation: a 31P magnetic resonance spectroscopy study at 4 Tesla. Sleep 37:1919-27
Trksak, George H; Bracken, Bethany K; Jensen, J Eric et al. (2013) Effects of sleep deprivation on brain bioenergetics, sleep, and cognitive performance in cocaine-dependent individuals. ScientificWorldJournal 2013:947879
Bracken, B K; Trksak, G H; Penetar, D M et al. (2012) Response inhibition and psychomotor speed during methadone maintenance: impact of treatment duration, dose, and sleep deprivation. Drug Alcohol Depend 125:132-9
Trksak, George H; Jensen, J Eric; Plante, David T et al. (2010) Effects of sleep deprivation on sleep homeostasis and restoration during methadone-maintenance: a [31]P MRS brain imaging study. Drug Alcohol Depend 106:79-91
Trksak, George H; Jensen, J Eric; Renshaw, Perry F et al. (2007) Brain phosphorus magnetic resonance spectroscopy imaging of sleep homeostasis and restoration in drug dependence. ScientificWorldJournal 7:217-22