Fructose:glucose ratios--a study of sugar self-administration and associated neural and physiological responses in the rat

Nutrients. 2015 May 22;7(5):3869-90. doi: 10.3390/nu7053869.


This study explored whether different ratios of fructose (F) and glucose (G) in sugar can engender significant differences in self-administration and associated neurobiological and physiological responses in male Sprague-Dawley rats. In Experiment 1, animals self-administered pellets containing 55% F + 45% G or 30% F + 70% G, and Fos immunoreactivity was assessed in hypothalamic regions regulating food intake and reward. In Experiment 2, rats self-administered solutions of 55% F + 42% G (high fructose corn syrup (HFCS)), 50% F + 50% G (sucrose) or saccharin, and mRNA of the dopamine 2 (D2R) and mu-opioid (MOR) receptor genes were assessed in striatal regions involved in addictive behaviors. Finally, in Experiment 3, rats self-administered HFCS and sucrose in their home cages, and hepatic fatty acids were quantified. It was found that higher fructose ratios engendered lower self-administration, lower Fos expression in the lateral hypothalamus/arcuate nucleus, reduced D2R and increased MOR mRNA in the dorsal striatum and nucleus accumbens core, respectively, as well as elevated omega-6 polyunsaturated fatty acids in the liver. These data indicate that a higher ratio of fructose may enhance the reinforcing effects of sugar and possibly lead to neurobiological and physiological alterations associated with addictive and metabolic disorders.

Keywords: dopamine 2 receptor; fatty acid; fructose; glucose; hepatic; hypothalamus; mu opioid receptor; nucleus accumbens; rat; self-administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Addictive / etiology
  • Brain / drug effects*
  • Dietary Carbohydrates / adverse effects
  • Dietary Carbohydrates / pharmacology*
  • Dietary Sucrose / pharmacology
  • Eating / drug effects*
  • Energy Intake / drug effects*
  • Fatty Acids, Omega-6 / metabolism
  • Feeding Behavior / drug effects*
  • Fructose / administration & dosage
  • Fructose / pharmacology*
  • Glucose / administration & dosage
  • Glucose / pharmacology*
  • High Fructose Corn Syrup / pharmacology
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Obesity / etiology
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism
  • Reward


  • Dietary Carbohydrates
  • Dietary Sucrose
  • Fatty Acids, Omega-6
  • High Fructose Corn Syrup
  • Oprm1 protein, rat
  • RNA, Messenger
  • Receptors, Dopamine D2
  • Receptors, Opioid, mu
  • Fructose
  • Glucose