Dopamine D(2/3) receptor availability in cocaine use disorder individuals with obesity as measured by [(11)C]PHNO PET

采用[(11)C]PHNO PET测量可卡因使用障碍合并肥胖患者的多巴胺D(2/3)受体可用性

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Abstract

BACKGROUND: Positron emission tomography (PET) work with the dopamine D3 receptor (D(3)R) preferring ligand [(11)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-[(11)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 [(11)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. [(11)C]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(2/3)R availability. This in contrast to previous findings in non-CUD individuals that found increased availability of D(3)Rs in the SN/VTA associated with obesity. These findings could potentially reflect dysregulation of D(3)R in CUD, impacting how affected individuals respond to natural stimuli such as food.

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