Fructose:glucose ratios–a study of sugar self-administration and associated neural and physiological responses in the rat (2015)

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

Levy A1, Marshall P2, Zhou Y3, Kreek MJ4, Kent K5, Daniels S6, Shore A7, Downs T8, Fernandes MF9, Mutch DM10, Leri F11.


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.


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

PMID: 26007337

PMCID: PMC4446784

DOI: 10.3390/nu7053869