Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity

Abstract

Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships between these variables and the impact of obesity on these relationships may reveal insight into the neurobiological basis of sweet preferences. We evaluated sucrose preferences, perception of sweetness intensity, and striatal D2R binding potential (D2R BPND) using positron emission tomography with a D2R-selective radioligand insensitive to endogenous dopamine, (N-[11C] methyl)benperidol, in 20 subjects without obesity (BMI 22.5 ± 2.4 kg/m2; age 28.3 ± 5.4 years) and 24 subjects with obesity (BMI 40.3 ± 5.0 kg/m2; age 31.2 ± 6.3 years). The groups had similar sucrose preferences, sweetness intensity perception, striatal D2R BPND, and age-related D2R BPND declines. However, both striatal D2R BPND and age correlated with sucrose preferences in subjects without obesity, explaining 52% of their variance in sucrose preference. In contrast, these associations were absent in the obese group. In conclusion, the age-related decline in D2R was not linked to the age-related decline in sweetness preferences, suggesting that other, as-yet-unknown mechanisms play a role and that these mechanisms are disrupted in obesity.

Challenges in the development of dopamine D2‐ and D3‐selective radiotracers for PET imaging studies

“…41 PET imaging studies of 11 C-and 18 F-N-methylbenperidol have been conducted in both nonhuman primates 42 and in a variety of CNS disorders. [43][44][45] The lower uptake of [ 11 C]N-methylbenperidol in the nucleus accumbens relative to the caudate and putamen is consistent with the distribution of D2 receptors in human brain. A minor limitation of [ 11 C/ 18 F]Nmethylbenperidol is its high affinity for dopamine D4 receptors; although the density of D4 receptors is low in the caudate, putamen, and nucleus accumbens, the D4 affinity could limit the imaging if extrastriatal D2 receptors because these regions contain both D2 and D4 receptors.…”

“…The most prominent example of this strategy is [ 11 C/ 18 F] N ‐methylbenperidol (Figure ), which has been shown to have a 200‐fold higher affinity for D2 versus D3 receptors . PET imaging studies of 11 C‐ and 18 F‐ N ‐methylbenperidol have been conducted in both nonhuman primates and in a variety of CNS disorders . The lower uptake of [ 11 C] N ‐methylbenperidol in the nucleus accumbens relative to the caudate and putamen is consistent with the distribution of D2 receptors in human brain.…”

Determinants of Sweetness Preference: A Scoping Review of Human Studies

“…Of note, in this study, both diet and caloric beverages were used, but only at a single strength/concentration, unlike the other studies in which there were four to 10 solutions tested that varied in their sweetness levels. In the other four adult studies, which included both females and males [75][76][77][78], there were no significant differences between the normal weight and overweight/obese groups in their sweetness preference; in three of these studies, sweetness preference was assessed using sucrose solutions, while in the study by Wooley et al [75], sweetness preference was assessed before and 1 h after ingestion of 200 mL of a 25% glucose solution or 200 mL of an isosweet cyclamate solution, on two different study days.…”

Sweet taste liking is associated with subjective response to amphetamine in women but not men

“…Specifically, neuroimaging studies indicate that both sweet taste and administration of a stimulant drug increase activity in the ventral striatum (Drevets et al 2001; Kareken et al 2013; Oswald et al 2005; Volkow et al 1999b). Additionally, D2 receptor availability predicts both subjective response to stimulant drugs (Volkow et al 1999a; Volkow et al 2002) and sucrose preference (Pepino et al 2016), such that fewer striatal D2 receptors are associated with greater stimulant drug reward and greater preference for sweet tastes. Given this overlap in reward pathways underlying both sweet taste and stimulant drug reward, it is possible that individuals who are more sensitive to sweet reward are also more sensitive to drug reward.…”