Elevated Dopamine D_2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [¹¹C](+)PHNO

Area of Science:

• Neuroscience
• Radiology
• Pharmacology

Background:

• Previous research using non-selective dopamine D2/3 receptor (D2/3R) antagonist tracers suggested lower D2/3R availability in obese individuals.
• A D3-preferring agonist tracer, [11C](+)PHNO, previously showed a positive association between body mass index (BMI) and D2/3R availability in striatal reward regions.
• Obese individuals had not yet been studied using the [11C](+)PHNO tracer.

Purpose of the Study:

• To assess D2/3R availability in striatal and extrastriatal reward regions of obese (OB) and normal weight (NW) individuals using [11C](+)PHNO PET.
• To investigate the linear association between BMI and D2/3R availability in specific brain regions within a larger cohort including overweight individuals.

Main Methods:

• Positron emission tomography (PET) scans were performed on 14 obese and 14 normal weight individuals using the D3-preferring agonist tracer [11C](+)PHNO.
• A high-resolution research tomograph was utilized for imaging.
• Secondary analyses included 42 overweight individuals to examine the association between BMI and D2/3R availability in regions with observed group differences.

Main Results:

• A significant group-by-brain region interaction was observed (F7,182=2.08, p=0.047).
• Obese individuals showed significantly higher tracer binding (higher D2/3R availability) in D3-rich regions: substantia nigra/ventral tegmental area (SN/VTA) (+20%, p=0.02), ventral striatum (VST) (+14%, p<0.01), and pallidum (+11%, p=0.02).
• Across all subjects, BMI was positively associated with D2/3R availability in the SN/VTA (r=0.34, p=0.03), VST (r=0.36, p=0.02), and pallidum (r=0.30, p=0.05).

Conclusions:

• Obese individuals exhibit higher D2/3R availability in key brain reward regions, particularly those rich in D3 receptors.
• The findings contradict previous studies using antagonist tracers and suggest a different role for D2/3R availability in obesity.
• These results identify a potential novel pharmacologic target for the treatment of obesity within specific dopamine receptor pathways.