title: Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers.
abstract: Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [(11)C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes.
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Wiers
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Shumay
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Cabrera
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Shokri-Kojori
authors.affiliation: Addiction Development and Psychopathology Lab, Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.|Research Centre-Military Mental Health, Ministry of Defense, Utrecht, The Netherlands.
authors.forename: T E
authors.initials: TE
authors.lastname: Gladwin
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: E
authors.initials: E
authors.lastname: Skarda
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S I
authors.initials: SI
authors.lastname: Cunningham
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T C
authors.initials: TC
authors.lastname: Wong
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Tomasi
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.
authors.forename: G-J
authors.initials: GJ
authors.lastname: Wang
authors.affiliation: National Institute on Alcohol Abuse and Alcoholism, Laboratory of Neuroimaging, National Institutes of Health, Bethesda, MD, USA.|National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.
authors.forename: N D
authors.initials: ND
authors.lastname: Volkow
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D019970:Cocaine-Related Disorders / Q000150:complications* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007407:Interviews as Topic; D008297:Male; D049268:Positron-Emission Tomography; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000150:complications* / Q000378:metabolism*; D013997:Time Factors
chemical_list: D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3