A comparison of D2 receptor specific binding in obese and normal‐weight individuals using PET with (N‐[¹¹C]methyl)benperidol

Abstract

Previous PET imaging studies have demonstrated mixed findings regarding dopamine D2/D3 receptor availability in obese relative to non-obese humans. Nonspecific D2/D3 radioligands do not allow for separate estimation of D2 receptor (D2R) and D3 receptor (D3R) subtypes of the D2 receptor family, which may play different roles in behavior and are distributed differently throughout the brain. These radioligands are also displaceable by endogenous dopamine, confounding interpretation of differences in receptor availability with differing levels of dopamine release. The present study used PET imaging with the D2R-selective radioligand (N-[11C] methyl)benperidol ([11C]NMB), which is non-displaceable by endogenous dopamine, to estimate D2R specific binding (BPND) and its relationship to body mass index (BMI) and age in 15 normal-weight (mean BMI = 22.6 kg/m2) and 15 obese (mean BMI = 40.3 kg/m2) men and women. Subjects with illnesses or taking medications that interfere with dopamine signaling were excluded. Striatal D2R BPND was calculated using the Logan graphical method with cerebellum as a reference region. D2R BPND estimates were higher in putamen and caudate relative to nucleus accumbens, but did not differ between normal-weight and obese groups. BMI values did not correlate with D2R BPND. Age was negatively correlated with putamen D2R BPND in both groups. These results suggest that altered D2R specific binding is not involved in the pathogenesis of obesity per se and underscore the need for additional studies evaluating the relationship between D3R, dopamine reuptake, or endogenous dopamine release and human obesity.

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

“…For instance, work with [ 11 C]raclopride has demonstrated reductions in striatal D 2/3 R availability in both severely obese ) and OB (Haltia et al, 2007) individuals when compared with NW controls. Complicating the picture further, [ 11 C]raclopride findings are not consistent with studies that utilized [ 11 C]FLB457, which demonstrated BMI was positively associated with amygdalar D 2/3 R availability (Yasuno et al, 2001) or [ 11 C] NMB, where no association between BMI and striatal D 2/3 R availability was found (Eisenstein et al, 2013). Such lack of agreement across the obesity and PET dopamine literature is complex and several factors could be responsible including differences in tracers and research participants.…”

“…This relationship did not extend to non-OB individuals, where no associations between striatal D 2/3 R availability and BMI have been found with [ 11 C]raclopride (Caravaggio et al, 2013). Work done with the D 2 -high affinity tracer, [ 11 C]N-methyl-benperidol (NMB), failed to show any striatal D 2/3 R availability alterations between NW and severely obese individuals (Eisenstein et al, 2013 . Other regions investigated with [ 18 F]fallypride have shown slightly higher D 2/3 R availability (not statistically significant) in the SN/VTA of OB as compared with NW females (Savage et al, 2014) and a positive linear association between D 2/3 R availability and BMI in the caudate and putamen of a large cohort of individuals with a wide BMI range (range 18-45 kg/m 2 ) (Guo et al, 2014).…”

Slave to habit? Obesity is associated with decreased behavioural sensitivity to reward devaluation

“…Moreover, DA is also released post-prandially, possibly mediating the successive devaluation of food reward during a meal (de Auraujo et al Neuron 2008) in addition to its release during anticipation and acute consumption of food rewards. Excessive eating, similar to chronic drug consumption, progressively leads to alterations in the dopaminergic system, specifically to a down-regulation of striatal dopamine 2 and/or 3 (D2/D3) receptors (De Weijer et al, 2011;Eisenstein et al, 2013;Geiger et al, 2009;Nader et al, 2006;Thanos, Michaelides, Benveniste, Wang, & Volkow, 2007;Wang et al, 2001). This down-regulation, among other factors, is assumed to induce a shift to cue-triggered habit-like consumption (Volkow et al, 2013).…”

Functional network centrality in obesity: A resting-state and task fMRI study

“…Relative to normal-weight participants, obese populations exhibit lower gray matter volume, cortical thickness and glucose metabolism in the prefrontal cortex (Pannacciulli et al, 2006;Willeumier et al, 2011;Marqués-Iturria et al, 2014). In striatal structures, individuals with obesity seem to exhibit lower dopamine D2/D3 receptor availability (Wang et al, 2001;De Weijer et al, 2011; but see Eisenstein et al, 2013) and increased gray matter volume . Additionally, functional neuroimaging studies have observed differences between participants with obesity and normal-weight controls during reward processing.…”