Dopamine D_2/3 receptor availability in cocaine use disorder individuals with obesity as measured by [¹¹C]PHNO PET

Background: Positron emission tomography (PET) work with the dopamine D3 receptor (D₃R) preferring ligand [¹¹C]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-[¹¹C]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 [¹¹C]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. [¹¹C]PHNO measures of receptor availability were calculated and expressed as non-displaceable binding potential (BP_ND).

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_ND 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 D_2/3R availability. This in contrast to previous findings in non-CUD individuals that found increased availability of D₃Rs in the SN/VTA associated with obesity. These findings could potentially reflect dysregulation of D₃R in CUD, impacting how affected individuals respond to natural stimuli such as food.