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The effects of medication-assisted treatment on D2R availability in patients with opioid use disorder and the contribution of sleep

Applicant Dr. Rui Zhang
Subject Area Human Cognitive and Systems Neuroscience
Term from 2018 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 405485320
 
Opioid use disorder (OUD) is a chronic relapsing disorder and has a high overdose death rate. Patients with OUD display severe impairments in cognitive control. Medication-Assisted Treatment (MAT) is suggested to help prevent risky behavior and drug relapse by improving cognitive control in OUD. Although poor cognitive control in OUD is strongly associated with low striatal dopamine D2 receptor (D2R) levels, it remains unclear whether MAT elevates striatal D2R availability and thereby enhances cognitive control in OUD. In addition, it has been demonstrated that MAT improves sleep quality in OUD and the effects of MAT depend on the sleep improvement. Reduced sleep duration and increased sleep disturbances are associated with decreased D2R availability. Based on the close relationship between sleep and D2R levels, it is likely that sleep mediates the effect of MAT on striatal D2R levels and thereby improves treatment efficacy. However, this has not yet been investigated.The proposed project aims to answer two questions 1) whether MAT contributes to cognitive control by elevating striatal D2R availability in OUD and 2) whether sleep duration and /or sleep quality mediates the effect of MAT on D2R levels. To investigate these questions, three groups of participants (OUD with MAT (MAT+ OUD), matched OUD without MAT (MAT- OUD) and healthy controls) will be compared on the following measurements: positron emission tomography (PET) scans with [11C]raclopride to assess striatal D2R availability, a backward inhibition paradigm and other neuropsychological tests are used to assess cognitive control and GENEActiv accelerometer is applied for objective sleep measures. Addressing these research questions will bring at least two advantages: 1) The current findings will contribute to overcoming the current barriers of utilizing MAT by clarifying the underlying neurobiological and neuropsychological effects of MAT. If MAT is shown to elevate striatal D2R availability, it may help reduce the stigma that MAT merely replaces one addiction with another. 2) The findings of the current study also have clinical implications. If sleep mediates the effects of MAT on D2R availability and neuropsychological performance, clinical interventions that improve sleep duration and quality may be beneficial for recovery in OUD.
DFG Programme Research Fellowships
International Connection USA
 
 

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