1. Dopamine D1 and D2 receptors are distinctly associated with rest-activity rhythms and drug reward.
- Author
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Zhang R, Manza P, Tomasi D, Kim SW, Shokri-Kojori E, Demiral SB, Kroll DS, Feldman DE, McPherson KL, Biesecker CL, Wang GJ, and Volkow ND
- Subjects
- Actigraphy, Adult, Central Nervous System Stimulants administration & dosage, Corpus Striatum physiology, Female, Humans, Male, Methylphenidate administration & dosage, Middle Aged, Motor Activity physiology, Positron-Emission Tomography, Rest physiology, Young Adult, Circadian Rhythm physiology, Receptors, Dopamine D1 physiology, Receptors, Dopamine D2 physiology, Reward, Substance-Related Disorders etiology, Substance-Related Disorders physiopathology
- Abstract
BACKGROUNDCertain components of rest-activity rhythms such as greater eveningness (delayed phase), physical inactivity (blunted amplitude), and shift work (irregularity) are associated with increased risk for drug use. Dopaminergic (DA) signaling has been hypothesized to mediate the associations, though clinical evidence is lacking.METHODSWe examined associations between rhythm components and striatal D1 (D1R) and D2/3 receptor (D2/3R) availability in 32 healthy adults (12 female, 20 male; age 42.40 ± 12.22 years) and its relationship to drug reward. Rest-activity rhythms were assessed by 1-week actigraphy combined with self-reports. [11C]NNC112 and [11C]raclopride positron emission tomography (PET) scans were conducted to measure D1R and D2/3R availability, respectively. Additionally, self-reported drug-rewarding effects of 60 mg oral methylphenidate were assessed.RESULTSWe found that delayed rhythm was associated with higher D1R availability in caudate, which was not attributable to sleep loss or so-called social jet lag, whereas physical inactivity was associated with higher D2/3R availability in nucleus accumbens (NAc). Delayed rest-activity rhythm, higher caudate D1R, and NAc D2/3R availability were associated with greater sensitivity to the rewarding effects of methylphenidate.CONCLUSIONThese findings reveal specific components of rest-activity rhythms associated with striatal D1R, D2/3R availability, and drug-rewarding effects. Personalized interventions that target rest-activity rhythms may help prevent and treat substance use disorders.TRIAL REGISTRATIONClinicalTrials.gov: NCT03190954.FUNDINGNational Institute on Alcohol Abuse and Alcoholism (ZIAAA000550).
- Published
- 2021
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