Original Investigation


, Volume 204, Issue 3, pp 431-443

First online:

Withdrawal from free-choice high-fat high-sugar diet induces craving only in obesity-prone animals

  • Chris PickeringAffiliated withDepartment of Neuroscience Functional Pharmacology, Uppsala University Email author 
  • , Johan AlsiöAffiliated withDepartment of Neuroscience Functional Pharmacology, Uppsala University
  • , Anna-Lena HultingAffiliated withDepartment of Endocrinology, Metabolism and Diabetology, Karolinska Institutet/Karolinska University Hospital-Solna
  • , Helgi B. SchiöthAffiliated withDepartment of Neuroscience Functional Pharmacology, Uppsala University

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access



Vulnerability for weight gain is an individual trait. Obese people undertake dieting, but permanent weight loss is difficult to attain due to repeated phases of relapse to excess consumption.

Materials and methods

In this study, male Wistar rats were trained to operantly self-administer pellets followed by free-choice access in the homecage to high-fat high-sugar (HFHS) diet consisting of 30% sucrose, lard, standard rodent chow and water. Animals were divided into obesity-prone (OP) and obesity-resistant (OR) groups based on relative weight gain compared to normally fed controls despite equal consumption of HFHS.

Results and discussion

After 4 weeks of HFHS access, OP and OR animals did not differ in motivation for food pellets in terms of progressive ratio break point, lever pressing or response rate. However, upon discontinuation of the HFHS diet, differences between the OP and OR groups were noted. OP animals increased their motivation (i.e. craving) during the second withdrawal week and reduced time spent in the centre of an open field (increased anxiety) compared to the OR animals. Both OP and OR animals consumed less of the standard rodent chow during the first week of withdrawal when compared to normally fed controls. But, while the OR animals quickly returned to control levels of food consumption, OP animals continued to consume less standard rodent chow.


The results show for the first time that withdrawal from free-choice HFHS induces craving that is specific to the OP animals and suggests that OP individuals may have withdrawal symptoms that are similar to those induced by addictive drugs.


Diet-induced obesity Operant self-administration Progressive ratio Fixed ratio Whole-animal physiology