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Conversations with a Neuron, Volume 3

Minipig’s Affliction is a Sucrose Addiction

This article provides new evidence that decreased binding of carfentanil in the nucleus accumbens and cingulate cortex occurs in Gottingen minipigs after exposure to sucrose.

Author: Ashley Vega-Lazaro

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Neurophysiology

In a paper recently published in Nature, Michael Winterdahl and associates investigate the relationship between sucrose and D2/3 availability, in Gottingen minipigs1. Current research on the addictive qualities of sucrose focuses on rats2,3. As studying sucrose consumption in humans is ethically and scientifically complicated, this data allows researchers to form hypotheses about the human response to sucrose. The data from the Gottingen minipigs translates better to the human brain and allows for better imaging of the brain in comparison to rats. The primary finding of this study was that sucrose intake lowers the availability of the dopamine receptors D2/3, in  addition to lowering the μ-opioid availability. This finding indicates that the usage of sucrose negatively impacts reward mechanisms similar to addictive drug usage.  

Background 

Obesity in the United States is increasing annually. In 2017-2018, the age-adjusted prevalence of obesity was 42.4% in adults4. Sucrose consumption is thought to play a direct role in the obesity numbers in the United States5. These increasing numbers in obesity and related health complications including heart disease enforce the need for further research about contributing factors6. Multiple metanalyses have previously examined the relationship between sugar consumption and obesity and found a positive correlation7,8. Previous research completed by Colantuoni and associates examined rats and found that dopamine (a neurotransmitter associated with reward) binding changes post sugar consumption. This rat study saw that after  30 days there was a marked increase in D1, and Opioid mu-1 receptors binding and a decrease in D2 receptors binding9. This was indication that similar changes should be seen in guinea pigs.  Another study completed by Avena and associates looked at sugar consumption in rats after 2 weeks of abstinence from glucose and found that the rats displayed the same addictive symptoms displayed immediately post daily exposure10. This indicates that the addiction was long lasting. These discoveries give credence to the idea of addiction similar to drug addiction being seen in minipigs after sucrose consumption.  

Methods 

Researchers imaged seven minipigs using raclopride and carfentanil initially and after 12 days of continuous sucrose intake. Sucrose exposure occurred for an hour daily for 12 consecutive days. 2 liters of sucrose was consumed daily by each minipig in their water. Positron emission tomography (PET) imaging which measures changes in metabolic processes and a low-dose computerized tomography (CT) scan that takes cross sectional images of the brain were utilized to image the minipig’s brains at baseline and after 12 day of sucrose exposure. The minipigs were euthanized after the final PET. Permutation theory and non-regionally restricted whole-brain analysis was used to analyze the results.

Figure 1: This figure shows a longitudinal section of a MRI scan with a binding potential map superimposed on top at baseline before exposure to sucrose, and after 12 days of exposure. The decrease in red after 12 days indicated that binding of carfentanil decreased.
Figure 1. This figure shows a longitudinal section of a MRI scan with a binding potential map superimposed on top at baseline before exposure to sucrose, and after 12 days of exposure. The decrease in red after 12 days indicated that binding of carfentanil decreased.

Results 

The minipigs gained an average of 13.6% body weight after 12 days of sucrose in comparison to a gain of 4.9% in the non-sucrose consuming control Guinea pigs studied. 5 of the minipigs imaged with carfentanil had a significant reduction in binding at the anterior cingulate cortex and the nucleus accumbens after the initial exposure to sucrose. The olfactory structures, prefrontal cortex, cingulate cortex, amygdala, and brainstem all were affected by the sucrose consumption after 12 days. This was seen in the PET scans showing reduced binding in these areas. 

Conclusion 

These findings are significant because it furthers the existing data on sucrose addiction. The images from the minipigs allows researchers to have a better understanding of the effects of sucrose on dopamine receptor binding. Additionally, these minipig brain scans reflects similar addictive qualities seen in rats/minipigs addicted to cocaine, and nicotine. This data will hopefully encourage researchers to study the impacts of sucrose and its relationship with addiction in humans. The current obesity rates, and health complications associated with obesity can be  decreased with more awareness on how consumption of added sugars is influencing our continued consumption and possible over consumption of certain foods.

 

[+] References

1.

Winterdahl, M., Noer, O., Orlowski, D., Schacht, A. C., Jakobsen, S., Alstrup, A., Gjedde,  A., & Landau, A. M. (2019). Sucrose intake lowers μ-opioid and dopamine D2/3 receptor  availability in porcine brain. Scientific reports, 9(1), 16918. https://doi.org/10.1038/s41598-019-53430-92.

2.

Hoebel, B. G., Avena, N. M., Bocarsly, M. E., & Rada, P. (2009). Natural addiction: a  behavioral and circuit model based on sugar addiction in rats. Journal of addiction  medicine, 3(1), 33–41. https://doi.org/10.1097/ADM.0b013e31819aa621.

3.

Lenoir, M., Serre, F., Cantin, L., & Ahmed, S. H. (2007). Intense sweetness surpasses  cocaine reward. PloS one, 2(8), e698. https://doi.org/10.1371/journal.pone.0000698.

4.

Products - Data Briefs - Number 360 - February 2020. (n.d.). CDC. https://www.cdc.gov/nchs/products/databriefs/db360.htm.

 

5.

Delli Bovi, A. P., Di Michele, L., Laino, G., & Vajro, P. (2017). Obesity and Obesity Related  Diseases, Sugar Consumption and Bad Oral Health: A Fatal Epidemic Mixtures: The  Pediatric and Odontologist Point of View. Translational medicine @ UniSa, 16, 11–16.

6.

Howard, B. V., & Wylie-Rosett, J. (2002). Sugar and cardiovascular disease: A statement  for healthcare professionals from the Committee on Nutrition of the Council on  Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation, 106(4), 523–527. https://doi.org/10.1161/01.cir.0000019552.77778.04.

 

7.

Faruque, S., Tong, J., Lacmanovic, V., Agbonghae, C., Minaya, D. M., & Czaja, K. (2019).  The Dose Makes the Poison: Sugar and Obesity in the United States - a Review. Polish  journal of food and nutrition sciences, 69(3), 219–233. https://doi.org/10.31883/pjfns/110735.

 

8.

Prinz, P. (2019). The role of dietary sugars in health: molecular composition or just  calories?. Eur J Clin Nutr 73, 1216–1223 https://doi.org/10.1038/s41430-019-0407-z.

9.

Colantuoni, C., Schwenker, J., McCarthy, J., Rada, P., Ladenheim, B., Cadet, J. L.,  Schwartz, G. J., Moran, T. H., & Hoebel, B. G. (2001). Excessive sugar intake alters  binding to dopamine and mu-opioid receptors in the brain. Neuroreport, 12(16), 3549– 3552. https://doi.org/10.1097/00001756-200111160-00035.

10.

Avena, N. M., Long, K. A., & Hoebel, B. G. (2005). Sugar-dependent rats show enhanced  responding for sugar after abstinence: evidence of a sugar deprivation effect. Physiology  & behavior, 84(3), 359–362. https://doi.org/10.1016/j.physbeh.2004.12.016.

[+] Other Work By Ashley Vega-Lazaro

Cerebellum at a junction, now there’s a function

Neuroanatomy

This article provides new evidence that the cerebellum, a structure located in the rear of the brain, has a larger role in controlling reward circuitry and social behavior than previously thought.