Dopamine D2/3 receptor availability in cocaine use disorder individuals with obesity as measured by [11C]PHNO PET

Drug Alcohol Depend. 2021 Mar 1;220:108514. doi: 10.1016/j.drugalcdep.2021.108514. Epub 2021 Jan 8.

Abstract

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 (BPND).

Results: In between-group analyses, D2/3R availability in non-obese and obese CUD groups was not significantly different overall. BMI was inversely correlated withBPND 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 D2/3R 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.

Keywords: Addictive behaviors; Cocaine; Dopamine; Obesity; Reward; Substance-related disorders.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Mass Index
  • Cocaine-Related Disorders / pathology*
  • Globus Pallidus / diagnostic imaging
  • Humans
  • Ligands
  • Middle Aged
  • Obesity / pathology*
  • Positron-Emission Tomography*
  • Receptors, Dopamine D2 / metabolism*
  • Receptors, Dopamine D3 / metabolism*
  • Substantia Nigra / diagnostic imaging
  • Ventral Tegmental Area / diagnostic imaging

Substances

  • Ligands
  • Receptors, Dopamine D2
  • Receptors, Dopamine D3