Journal of Food Science and Technology

, Volume 57, Issue 1, pp 113–121 | Cite as

Effects of different sweeteners on behavior and neurotransmitters release in mice

  • Kai-Jing Yin
  • Ding-Yuan Xie
  • Lei Zhao
  • Gang FanEmail author
  • Jing-Nan Ren
  • Lu-Lu Zhang
  • Si-Yi Pan
Original Article


Four natural sweeteners (sucrose, stevioside, maltose and xylitol) and six artificial sweeteners (acesulfame, sucralose, aspartame, cyclamate, saccharin and neotame) were used to study the effects of different sweeteners on the behavior and neurotransmitter release of mice with two-bottle preference experiments. The results showed that very significant preference behavior for 8% sucrose solution, 0.3% stevioside solution, 10 mM acesulfame, 10 mM sucralose and 10 mM aspartame solutions (p < 0.01) was observed on mice. Long-term exposure of sucrose solution and acesulfame solution can affect the behavioral indicators such as solution consumption, feed intake, body weight and the release of neurotransmitters in mice. The solution consumption and the release of neurotransmitters were significantly greater (p < 0.05) than that of the control group (water group), but there was no significant difference in feed intake. The acesulfame-A and acesulfame-B groups had no significant difference on the consumption of solution and feed intake, but there was significant difference in the release of neurotransmitters. The result also showed that different sweetener solutions with similar sweetness had the same effect on the neurotransmitters release, and it can be inferred that mice have an addictive behavioral characteristic to sucrose.


Sweeteners Two-bottle preference test Neurotransmitters Mice 



This study was supported by the National Key Research and Development Plan of China (2017YFD0400101), National Natural Science Foundation of China (Program No. 31671824).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abhilash M, Paul MVS, Varghese MV, Nair RH (2013) Long-term consumption of aspartame and brain antioxidant defense status. Drug Chem Toxicol 36(2):135–140CrossRefGoogle Scholar
  2. Andrews CM, Lucki I (2001) Effects of cocaine on extracellular dopamine and serotonin levels in the nucleus accumbens. Psychopharmacology 155(3):221–229CrossRefGoogle Scholar
  3. Avena NM, Rada P, Moise N, Hoebel BG (2006) Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response. Neuroscience 139(3):813–820CrossRefGoogle Scholar
  4. Avena NM, Rada P, Hoebel BG (2008) Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32(1):20–39CrossRefGoogle Scholar
  5. Bachmanov AA, Tordoff MG, Beauchamp GK (2001) Sweetener preference of C57BL/6ByJ and 129P3/J mice. Chem Senses 26(7):905–913CrossRefGoogle Scholar
  6. Bandyopadhyay A, Ghoshal S, Mukherjee A (2008) Genotoxicity testing of low-calorie sweeteners: aspartame, acesulfame-K, and saccharin. Drug Chem Toxicol 31:447–457CrossRefGoogle Scholar
  7. Bian XM, Chi L, Gao B, Tu P, Ru H, Lu K (2017) The artificial sweetener acesulfame potassium affects the gut microbiome and body weight gain in CD-1 mice. PLoS ONE 12(6):e0178426CrossRefGoogle Scholar
  8. Burke MV, Small DM (2015) Physiological mechanisms by which non-nutritive sweeteners may impact body weight and metabolism. Physiol Behav 152:381–388CrossRefGoogle Scholar
  9. Chi L, Bian X, Gao B, Tu P, Lai Y, Ru H, Lu K (2018) Effects of the artificial sweetener neotame on the gut microbiome and fecal metabolites in mice. Molecules 23:367CrossRefGoogle Scholar
  10. De Araujo IE, Oliveira-Maia AJ, Sotnikova TD, Gainetdinov RR, Caron MG, Nicolelis MAL, Simon SA (2008) Food reward in the absence of taste receptor signaling. Neuron 57(6):930–941CrossRefGoogle Scholar
  11. Duffey KJ, Steffen LM, Van Horn L, Jacobs DR Jr, Popkin BM (2012) Dietary patterns matter: diet beverages and cardiometabolic risks in the longitudinal Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Clin Nutr 95:909–915CrossRefGoogle Scholar
  12. Fowler SP, Williams K, Hazuda HP (2015) Diet soda intake is associated with long-term increases in waist circumference in a biethnic cohort of older adults: the San Antonio longitudinal study of aging. J Am Geriatr Soc 63:708–715CrossRefGoogle Scholar
  13. Garber AK, Lustig RH (2011) Is fast food addictive? Curr Drug Abuse Rev 4:146–162CrossRefGoogle Scholar
  14. Gardner C, Wylie-Rosett J, Gidding SS, Steffen LM, Johnson RK, Reader D, Lichtenstein AH (2012) Non-nutritive sweeteners: current use and health perspectives: a scientific statement from the American heart association and the American diabetes association. Circulation 126:509–519CrossRefGoogle Scholar
  15. Guo HL (2013) The biological basis research of sweet perception in oral cavity and intestine of mice after preference sweetness exposure. Zhejiang Gongshang University, HangzhouGoogle Scholar
  16. Hamada FN, Rosenzweig M, Kang K, Pulver SR, Ghezzi A, Jegla TJ, Garrity PA (2008) An internal thermal sensor controlling temperature preference in Drosophila. Nature 454(7501):217–220CrossRefGoogle Scholar
  17. Kuk JL, Brown RE (2016) Aspartame intake is associated with greater glucose intolerance in individuals with obesity. Appl Physiol Nutr Metab 41:795–798CrossRefGoogle Scholar
  18. Liauchonak I, Qorri B, Dawoud F, Riat Y, Szewczuk MR (2019) Non-nutritive sweeteners and their implications on the development of metabolic syndrome. Nutrients 11(3):644CrossRefGoogle Scholar
  19. Lustig RH (2010) Fructose: metabolic, hedonic, and societal parallels with ethanol. J Am Diet Assoc 110(9):1307–1321CrossRefGoogle Scholar
  20. Mao WF, Song Y (2018) Major problems and hazards in use of sweeteners commonly found in foods. J Food Sci Technol 36(6):9–14Google Scholar
  21. Miller PE, Perez V (2014) Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. Am J Clin Nutr 100(3):765–777CrossRefGoogle Scholar
  22. Nishida C, Uauy R, Kumanyika S, Shetty P (2004) The joint WHO/FAO expert consultation on diet and the prevention of chronic diseases: process, product and policy implications. Public Health Nutr 7(1A):245–250CrossRefGoogle Scholar
  23. Noorjahan A, Amrita B, Kavita S (2014) In vivo evaluation of taste masking for developed chewable and orodispersible tablets in humans and rats. Pharm Dev Technol 19(3):290–295CrossRefGoogle Scholar
  24. Peters JC, Beck J, Cardel M, Wyatt HR, Foster GD, Pan Z, Wojtanowski AC, Vander-Veur SS, Herring SJ, Brill C, Hill JO (2016) The effects of water and non-nutritive sweetened beverages on weight loss and weight maintenance: a randomized clinical trial. Obesity 24:297–304CrossRefGoogle Scholar
  25. Petro AE, Cotter J, Cooper DA, Peters JC, Surwit SJ, Surwit RS (2004) Fat, carbohydrate, and calories in the development of diabetes and obesity in the C57BL/6J mouse. Metabolism 53(4):454–457CrossRefGoogle Scholar
  26. Sclafani A, Touzani K, Bodnar RJ (2011) Dopamine and learned food preferences. Physiol Behav 104:64–68CrossRefGoogle Scholar
  27. Seiden LS, Sabol KE, Ricaurte GA (1993) Amphetamine: effects on catecholamine systems and behavior. Annu Rev Pharmacol Toxicol 33:639–677CrossRefGoogle Scholar
  28. Sun C, Liu J (2018) Modern food hygiene. People’s Medical Publishing House, BeijingGoogle Scholar
  29. Talukdar S, Owen BM, Song P, Hernandez G, Zhang Y, Zhou Y, Scott WT, Paratala B, Turner T, Smith A, Bernardo B, Müller CP, Tang H, Mangelsdorf DJ, Goodwin B, Kliewer SA (2016) FGF21 regulates sweet and alcohol preference. Cell Metab 23:344–349CrossRefGoogle Scholar
  30. Wang QP, Lin YQ, Zhang L, Wilson YA, Oyston LJ, Cotterell J, Qi Y, Khuong TM, Bakhshi N, Planchenault Y, Browman DT, Lau MT, Cole TA, Wong AC, Simpson SJ, Cole AR, Penninger JM, Herzog H, Neely GG (2016) Sucralose promotes food intake through NPY and a neuronal fasting response. Cell Metab 24(1):75–90CrossRefGoogle Scholar
  31. Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94(4):469–492CrossRefGoogle Scholar
  32. Wong DL (2006) Epinephrine biosynthesis: hormonal and neural control during stress. Cell Mol Neurobiol 26(4–6):889–898CrossRefGoogle Scholar
  33. Zhao DY, Huang PH, Cao JQ, Sun W, Han XL, Wang DL (2019) Effects of sesame aroma Baijiu on drinking behavior and dopamine neurotransmitter Levels in mice. Liquor Mak Sci Technol 4:55–60Google Scholar
  34. Zukerman S, Ackroff K, Sclafani A (2013) Post-oral glucose stimulation of intake and conditioned flavor preference in C57BL/6J mice: a concentration-response study. Physiol Behav 109:33–41CrossRefGoogle Scholar

Copyright information

© Association of Food Scientists & Technologists (India) 2019

Authors and Affiliations

  1. 1.College of Food Science and Technology, Huazhong Agricultural University, Key Laboratory of Environment Correlative DietologyMinistry of EducationWuhanChina
  2. 2.Food and Agriculture Standardization InstituteChina National Institute of StandardizationBeijingChina

Personalised recommendations