Sugar-addictive phenotypes in mice

Hyper palatable food rich in sugar and/or fat induces addictive symptoms in a proportion of obese people, though the term “food addiction” currently remains controversial. Recently, the new psychiatric classification system DSM-V has for the first time categorized drug addiction vs behavioral addiction, and their central definition is dependence on a substance or activity. A critical factor contributing to this uncertainty is the lack of an appropriate animal model investigating the addictive potential of food and their similarities with drug addiction. This study was designed to prove whether sugar, a main component in highly palatable food, is genuinely addictive or not. Fourteen female mice was trained with an operant self-administration paradigm (37 weeks) with fixed ratio (FR) 1 and FR 4 to establish 3-crit animal model which has already been established with Cocaine [1], in between phenotypes like the activity pattern, seeking, craving, motivation, anxiety level and sugar metabolism patterns monitored. Here, 3 tests (Time-out test, Progressive ratio test and Quinine solution test) were utilized to mimic the 3 criteria (High persistence in responding even on consequences, High motivation and Continuing intake despite negative consequences) concluded from the DSM diagnostic standards. What is more, a relapse test was performed to monitor a sugar deprivation effect. Male and female mice (n=20 or 11) were exposed to 5% sugar for 8 weeks in a continuous (24 h daily, 7 days per week) or intermittent (2 h daily, 5 days per week) way, and they were re-exposed to sugar solution after withdrawing the sugar solution for 15 days [2]. Our data proposed that chronic sugar exposure led to addictive phenotypes and a deprivation effect. In the 3-crit experiment, there was an intake escalation in female mice from the beginning of training to 40 sessions and then their intake stayed stable. The percentage of 3-crit animals has risen from 7% after 10 weeks to 14% after 20 weeks, staying at 14% after 27 weeks approximate to the proportion (15%-17%) of fully cocaine-addicted individuals in the human population who are initially exposed to drugs [1]. The Cue light and priming (a drop of 3% sucrose solution) induced the reinstatement of seeking behavior after extinction, and there was an incubation effect after 35 days of abstinence. Besides, long-term operant sugar exposure altered sucrose metabolism patterns and circadian rhythm of homecage activity, not anxiety levels. Results of the relapse study showed that there was a sugar deprivation effect in continuously but intermittently sugar-exposed mice, and relapse to sugar is stronger and longer in female compared to in male. This study indicated sugar has similar addictive properties as drugs of abuse, like Cocaine and Alcohol as demonstrated with 3-crit animal model in female mice and the relapse test. This project will be important for understanding the neurobiological basis of binge eating, sugar addiction and metabolic syndrome.