Dopamine D receptor availability in cocaine use disorder individuals with obesity as measured by [C]PHNO PET.

Background: Positron emission tomography (PET) work with the dopamine D3 receptor (DR) preferring ligand [C]PHNO in obese individuals has demonstrated higher binding and positive correlations with body mass index (BMI) in otherwise healthy individuals. These findings implicated brain reward areas including the substantia nigra/ventral tegmental area (SN/VTA) and pallidum. In cocaine use disorder (CUD), similar SN/VTA binding profiles have been found compared to healthy control subjects. This study investigates whether BMI-[C]PHNO relationships are similar in individuals with CUD.

Methods: Non-obese CUD subjects (N = 12) were compared to age-matched obese CUD subjects (N = 14). All subjects underwent [C]PHNO acquisition using a High Resolution Research Tomograph PET scanner. Parametric images were computed using the simplified reference tissue model with cerebellum as the reference region. [C]PHNO measures of receptor availability were calculated and expressed as non-displaceable binding potential (BP).

Results: In between-group analyses, D2/3R availability in non-obese and obese CUD groups was not significantly different overall. BMI was inversely correlated withBP in the SN/VTA (r = -0.45, p = 0.02 uncorrected) in all subjects.

Conclusion: These data suggest that obesity in CUD was not associated with significant differences in DR availability. This in contrast to previous findings in non-CUD individuals that found increased availability of DRs in the SN/VTA associated with obesity. These findings could potentially reflect dysregulation of DR in CUD, impacting how affected individuals respond to natural stimuli such as food.