Behaviour and Neural Indices of the Abuse Liability associated with Intraoral Self-administration of High Fructose Corn Syrup
Bibliographic record
Abstract
Food addiction (FA) is characterized by addictive behaviours including compulsively eating and neurobiological alterations that emerge in response to consuming food. Evidence strongly suggests sucrose is addictive; however, this sweetener has been almost entirely replaced by high fructose corn syrup (HFCS) in food/drink. Interestingly, HFCS impairs metabolic function and its introduction into the food supply is linked to the emergence of a concurrent epidemic of obesity; yet, little is known about its addictive properties. Therefore, we investigated its abuse liability and characterized these effects relative to sucrose. Using a novel procedure for sugar self-administration (SA), intraoral SA (IOSA) of HFCS was concentration dependent and supported by caloric content. Repeated IOSA led to escalation of intake, bingeing, and enhanced motivation to lever-press, indicating HFCS is reinforcing and possesses abuse liability. Moreover, compared to sucrose, HFCS alters expression of dopamine-2 (D2R) and mu-opioid (MOR) receptor mRNA in a manner putatively associated with exposure to drugs of abuse and the development of addiction. This occurred despite lower levels of HFCS SA, suggesting it may have more potent reinforcing effects and greater abuse liability. Likewise, SA of pellets mimicking HFCS engendered less hypothalamic activation than sucrose; in line with evidence that high fructose sugars may contribute to poor appetite regulation and possibly excessive intake. Bupropion (BUP) and naltrexone (NTX) were investigated with respect to their ability to reduce HFCS SA when administered alone, because they diminish the reinforcing properties of abused drugs, and in combination (BUP+NTX), to mimic the pharmacological actions of Contrave®, used to enhance weight-loss. BUP+NTX and NTX reduced IOSA of HFCS and upregulated expression of anorexigenic pro-opiomelanocortin mRNA in the hypothalamus. Moreover, compared to drugs of abuse or IOSA of HFCS alone, the addition of BUP+NTX led to opposing effects on DR2 and MOR mRNA expression, suggesting novel applications for Contrave® in treating FA or substance related abuse disorders. Together, these studies provide novel evidence that HFCS is addictive and support adopting policies that may limit its availability to reduce the potential harm associated with HFCS consumption as well as curb rising rates of obesity in vulnerable individuals.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".