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Cortical D1 and D2 dopamine receptor availability modulate methylphenidate-induced changes in brain activity and
Peter Manza1, Ehsan Shokri-Kojori2, Şükrü Barış Demiral2
1National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. peter.manza@nih.gov.
Communications Biology
|May 31, 2022
Summary
The balance of dopamine D1 and D2 receptors in the brain influences cognitive function and how methylphenidate affects brain activity. Higher D1 to D2 receptor ratios in association cortices are linked to better working memory and less age-related decline.
Area of Science:
- Neuroscience
- Cognitive Neuroscience
- Pharmacology
Background:
- Dopamine signaling is crucial for brain network organization and behavior.
- The balance between dopamine D1 receptors (D1R) and D2 receptors (D2R) is theorized to modulate excitatory and inhibitory signaling, impacting cognition.
- The precise role of the D1R to D2R balance in coordinating human brain functional networks remains unclear.
Purpose of the Study:
- To investigate how the ratio of cortical dopamine D1R to D2R signaling influences brain functional network activity and connectivity.
- To examine the effects of methylphenidate, a dopamine-boosting drug, on brain function in relation to D1R-D2R ratios.
- To explore the association between D1R-D2R ratios, cognitive performance (spatial working memory), and aging.
Main Methods:
- Collected PET and fMRI data from 36 healthy adults.
- Administered methylphenidate or placebo in a blinded, counterbalanced design to assess dopamine's effects.
- Quantified D1R and D2R availability and measured brain activity (fALFF) and resting-state functional connectivity.
Main Results:
- The D1R to D2R ratio was higher in association cortices than sensorimotor cortices.
- Methylphenidate increased brain activity in association cortices and decreased it in sensorimotor cortices.
- The D1R-D2R ratio, not individual receptor availability, correlated positively with working memory and negatively with age in association cortices.
Conclusions:
- Dopamine-boosting drugs like methylphenidate differentially affect brain regions based on their D1R-D2R balance.
- Regions with higher D2R (sensorimotor) showed greater activity and connectivity decreases under methylphenidate compared to D1R-rich regions (association cortices).
- A balanced D1R-D2R interaction in association cortices is vital for cognitive function and is impacted by aging.
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