Isojärvi, J. | bioRxiv Science

bioRxiv2021

Age and sex dependent variability of type 2 dopamine receptors in the human brain: A large-scale PET cohort

BACKGROUNDThe dopamine system contributes to a multitude of functions ranging from reward and motivation to learning and movement control, making it a key component in goal-directed behavior. Altered dopaminergic function is observed in neurological and psychiatric conditions. Numerous factors have been proposed to influence dopamine function, but due to small sample sizes and heterogeneous data analysis methods in previous studies their specific and joint contributions remain unresolved. METHODSIn this cross-sectional register-based study we investigated how age, sex, body mass index (BMI), as well as cerebral hemisphere and regional volume influence striatal type 2 dopamine receptor (D2R) availability in the human brain. We analyzed a large historical dataset (n=156, 120 males and 36 females) of [11C]raclopride PET scans performed between 2004 and 2018. RESULTSStriatal D2R availability decreased through age for both sexes and was higher in females versus males throughout age. BMI and striatal D2R availability were weakly associated. There was no consistent lateralization of striatal D2R. The observed effects were independent of regional volumes. These results were validated using two different spatial normalization methods, and the age and sex effects also replicated in an independent sample (n=135). CONCLUSIONSD2R density is dependent on age and sex, which may contribute to the vulnerability of neurological and psychiatric conditions involving altering D2R expression.

neuroscience↗

bioRxiv2020

Cerebral μ-opioid and CB1-receptor systems have distinct roles in human feeding behavior

Eating behavior varies greatly between healthy individuals, but the neurobiological basis of these trait-like differences in feeding remains unknown. Central {micro}-opioid receptors (MOR) and cannabinoid CB1-receptors (CB1R) regulate energy balance via multiple neural pathways, promoting food intake and reward. Because obesity and eating disorders have been associated with alterations in the brains opioid and endocannabinoid signaling, the variation in MOR and CB1R system function could potentially underlie distinct eating behavior phenotypes. In this retrospective positron emission tomography (PET) study, we analyzed [11C]carfentanil PET scans of MORs from 92 healthy subjects (70 males and 22 females), and [18F]FMPEP-d2 scans of CB1Rs from 35 subjects (all males, all also included in the [11C]carfentanil sample). Eating styles were measured with the Dutch Eating Behavior Questionnaire (DEBQ). We found that lower cerebral MOR availability was associated with increased external eating - individuals with low MORs reported being more likely to eat in response to environments palatable food cues. CB1R availability was associated with multiple eating behavior traits. We conclude that although MORs and CB1Rs overlap anatomically and functionally in the brain, they have distinct roles in mediating individual feeding patterns.

neuroscience↗