Optimal interpretation of pleasurable, rewarding experiences favors decisions that enhance survival. However, pleasure seeking can also lead to deleterious and life- threatening behaviors, exemplified by abusive drug addiction, impulsive thrill seeking and adverse risk taking. These reward mechanisms are supported, in part, by activity in dopamine pathways of the brain, including the ventral tegmental nuclei and striatum. One circumstance increasingly related to altered dopaminergic brain reward sensitivity is the state of sleep deprivation. Sleep loss can trigger amplified reactivity in dopaminergic networks in response to pleasurable experiences, elevate levels of dopamine within these circuits, and further enhance dopamine receptor sensitivity throughout these networks. Despite such emerging evidence, the impact of sleep loss on human brain reward processing and associated behaviors remains largely uncharacterized. Furthermore, the degree to which these neural and behavioral processes can be restored by recovery sleep, following deprivation, is similarly unknown. The need to characterize this potentially causal interaction is worthy of attention considering the known disruption of sleep in numerous addiction disorders associated with altered reward brain activity. Identifying such an interaction would implicate sleep loss as a predisposing risk factor in heightened responsivity and hence addiction potential to reward-stimulating drugs. It would further indicate a role for sleep disruption in the maintenance of addiction habits, especially during attempted withdrawal. Using functional MRI scanning in combination with established reward paradigms and sleep physiological recordings, here we propose to test the central hypothesis that (i) sleep deprivation amplifies sensitivity of the huma dopaminergic system in response to reward incentives, which additionally (ii) biases the brain towards disproportionate hippocampal reward-driven learning, and (iii) one night of recovery sleep, following deprivation, is sufficient to restore optimal functioning of these neural and behavioral reward processes. Therefore, this R21 proposal represents a systematic evaluation of how sleep loss and sleep recovery causally amplify human brain reward sensitivity, altering associated behaviors, and whether such dysfunction is reversed by recovery sleep. Considering the high prevalence and comorbidity of sleep disruption in addiction disorders, the proposed research holds substantive and direct clinical as well as broad public-health ramifications, with logical next-step translational targets.

Public Health Relevance

This proposal represents a systematic evaluation of how sleep loss may causally amplify human brain reward sensitivity;maladaptively altering associated behaviors, and whether such dysfunction is reversed by recovery sleep. Considering the high prevalence and comorbidity of sleep disruption in addiction disorders, the proposed research holds substantive and direct clinical as well as broad public- health ramifications, with logical next-step translational targets. Moreover, considering the continued erosion of sleep time across society, particularly in young populations additionally susceptible to reward and addiction difficulties, the applicability of these studies further increases in relevance.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DA031939-02
Application #
8458528
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Gordon, Harold
Project Start
2012-05-01
Project End
2014-03-31
Budget Start
2013-04-01
Budget End
2014-03-31
Support Year
2
Fiscal Year
2013
Total Cost
$198,783
Indirect Cost
$53,244
Name
University of California Berkeley
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Saletin, Jared M; Goldstein-Piekarski, Andrea N; Greer, Stephanie M et al. (2016) Human Hippocampal Structure: A Novel Biomarker Predicting Mnemonic Vulnerability to, and Recovery from, Sleep Deprivation. J Neurosci 36:2355-63
Goldstein-Piekarski, Andrea N; Greer, Stephanie M; Saletin, Jared M et al. (2015) Sleep Deprivation Impairs the Human Central and Peripheral Nervous System Discrimination of Social Threat. J Neurosci 35:10135-45
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Abel, Ted; Havekes, Robbert; Saletin, Jared M et al. (2013) Sleep, plasticity and memory from molecules to whole-brain networks. Curr Biol 23:R774-88