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Understanding the Neurobiology of Drug Addiction by Studying Sleep Disturbances and Circadian Rhythms

Minisymposium at the Annual Meeting of the Society for Neuroscience
Convention Center
San Diego, California
November 5, 2007

NIDA Organizer(s):
Harold W. Gordon, Ph.D.

Meeting Purpose and Intent:

To present data that demonstrate the interrelatedness of sleep, sleep disturbances, and circadian rhythms with neurological diseases including drug addiction.

Meeting participants were asked to address one of three broad areas of research – the effects of drugs of abuse on:

  1. Circadian rhythms at the molecular and behavioral level in rodents;
  2. Sleep architecture as assessed by polysomnogram and behavior in humans; and/or
  3. Sleep deprivation and biological sleep mechanisms.

Brief Discussion of Meeting Outcome:

Presentations focused on:

Colleen McClung, Ph.D., University of Texas Southwestern; Circadian Rhythms, Genes and Drug Addiction. Many circadian genes are regulated by drugs like cocaine--CLOCK and NPAS2 act as transcriptional regulators in the mesolimbic DA circuit between the VTA and NAc.

Ann Kosobud, Ph.D., Indiana University Medical School; Drugs of Abuse Entrain Circadian Rhythms. Drugs of abuse–ethanol, fentanyl, nicotine–entrain wheel-running in rats controlled by a circadian timer and may be mediated by mechanisms common to feeding and drug addiction.

Michael Irwin, M.D., University of California, Los Angeles; Sleep and Cytokines in Cocaine Dependence. Cocaine dependent patients show prolonged sleep latency and loss of delta sleep, a decreased capacity of monocytes to express TNF-alpha and IL-6, and substantially different cytokine expression just prior to sleep onset, through the night, but not day.

George Trksak, Ph.D., McLean Hospital, Harvard University; Changes in Brain Energy Using Magnetic Resonance Spectroscopy as a Measure of Sleep Homeostasis in Methadone-Maintained and Healthy Control Subjects. MR spectroscopy shows short-term (<1 yr) methadone-maintained patients fail to regain energy phosphates, phosphocreatine and beta-nucleoside triphosphate, during recovery after sleep deprivation and experience reduced sleep efficiency.

Una D. McCann, M.D., The Johns Hopkins School of Medicine; Alterations of Sleep and Other Behaviors Modulated by Serotonin and Catecholamines in Users of MDMA as Assessed by Catecholamine Depletion by AMPT. MDMA users demonstrate differentially-altered sleep, cognitive function and impulsivity, exacerbated by AMPT-depleted catecholamines, suggesting that MDMA-induced changes in the neurobiology of sleep may underlie cognitive deficits in MDMA users.

Peter Morgan, M.D., Ph.D., Yale University School of Medicine; Sleep and Cognitive Deficits in Abstinent Cocaine Patients. In abstinent cocaine patients, vigilance and learning are deficient as is sleep EEG while subjectively, improving sleep is reported. Reward and arousal circuits are likely involved in this disconnect.

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