Sucrose intake lowers μ-opioid and dopamine D2/3 receptor availability in porcine brain

Abstract

Excessive sucrose consumption elicits addiction-like craving that may underpin the obesity epidemic. Opioids and dopamine mediate the rewarding effects of drugs of abuse, and of natural rewards from stimuli such as palatable food. We investigated the effects of sucrose using PET imaging with [11C]carfentanil (μ-opioid receptor agonist) and [11C]raclopride (dopamine D2/3 receptor antagonist) in seven female anesthetized Göttingen minipigs. We then gave minipigs access to sucrose solution for one hour on 12 consecutive days and performed imaging again 24 hours after the final sucrose access. In a smaller sample of five minipigs, we performed an additional [11C]carfentanil PET session after the first sucrose exposure. We calculated voxel-wise binding potentials (BPND) using the cerebellum as a region of non-displaceable binding, analyzed differences with statistical non-parametric mapping, and performed a regional analysis. After 12 days of sucrose access, BPND of both tracers had declined significantly in striatum, nucleus accumbens, thalamus, amygdala, cingulate cortex and prefrontal cortex, consistent with down-regulation of receptor densities. After a single exposure to sucrose, we found decreased binding of [11C]carfentanil in nucleus accumbens and cingulate cortex, consistent with opioid release. The lower availability of opioid and dopamine receptors may explain the addictive potential associated with intake of sucrose.

Fetal Programming by Methyl Donors Modulates Central Inflammation and Prevents Food Addiction-Like Behavior in Rats

“…In line with this evidence, humans have shown increased caloric food liking and/or increased hunger ratings in subjects classified as food addicts (Loxton and Tipman, 2017;Ruddock et al, 2017). Mechanistically, it has been proposed that excessive high-energy food consumption seems to negatively modulate a hedonic phenotype in animal models (Kenny, 2011;Barry et al, 2018;Ducrocq et al, 2019), in part, by downregulating the D2 dopamine receptors (Johnson and Kenny, 2010;Winterdahl et al, 2019), and/or reduced dopamine release (Avena and Bocarsly, 2012). In our context, it seems FIGURE 7 | Demethylation inhibits microglia phagocytosis in microglia cells.…”

Western diet, obesity and bariatric surgery sequentially modulated anxiety, eating patterns and brain responses to sucrose in adult Yucatan minipigs

“…We must reckon though that the behavioral criteria for addiction were not met in this study. Our brain imaging results are consistent with the results showed by Winterdahl and collaborators 37 , who found that chronic exposure to sucrose reduced D2/ D3 dopamine receptors and µ-opioid receptors availability in Göttingen minipigs' prefrontal cortex, cingulated and striatum. The D2/D3 receptors support an inhibiting message, and a lack of these D2-like receptor result in altered inhibition in goal-directed behaviour.…”

The role of mu-opioids for reward and threat processing in humans: Bridging the gap from preclinical to clinical opioid drug studies

“…Inhibition of mu-opioid signalling prevented newborn mice (Moles et al, 2004) and lambs (Shayit et al, 2003) from developing a behavioural preference for their mother, highlighting the importance of opioid signals for social bond formation in these animals. Moreover, a study of five miniature pigs that were given an hour's access to sweet foods was broadly consistent with rodent work, indicating putative reward-related opioid release in the pig NAc (Winterdahl et al, 2019). Whereas in cats, opioid antagonism reduced cats' engagement with catnip-like substances, putatively due to blockade of its intrinsic reward value (Uenoyama et al, 2021).…”