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Withdrawal from free-choice high-fat high-sugar diet induces craving only in obesity-prone animals
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
Department of Endocrinology, Metabolism and Diabetology, Karolinska Institutet, Stockholm.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
2009 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 204, no 3, 431-443 p.Article in journal (Refereed) Published
Abstract [en]


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.


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.


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.

Place, publisher, year, edition, pages
2009. Vol. 204, no 3, 431-443 p.
Keyword [en]
Diet-induced obesity, Operant self-administration, Progressive ratio, Fixed ratio, Whole-animal physiology
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-117600DOI: 10.1007/s00213-009-1474-yISI: 000266085700006PubMedID: 19205668OAI: oai:DiVA.org:uu-117600DiVA: diva2:300943
Available from: 2010-03-01 Created: 2010-02-21 Last updated: 2011-12-02Bibliographically approved
In thesis
1. From Food Preference to Craving: Behavioural Traits and Molecular Mechanisms
Open this publication in new window or tab >>From Food Preference to Craving: Behavioural Traits and Molecular Mechanisms
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Preference for palatable and energy-dense foods may be a risk factor for body weight gain and has both genetic and environmental components. Once obesity develops in an individual, weight loss is difficult to achieve. Indeed, obesity is often characterized by repeated attempts to reduce the overconsumption of energy-dense foods, followed by food craving and relapse to overconsumption. Relapse and loss of control over intake are observed also in drug addicts, and it has been shown that obesity and drug addiction not only share behavioural features but also neural circuitry, e.g. the mesolimbic dopamine pathway. In this thesis, we sought to investigate the mechanisms related to food preferences and craving using animal models previously used in addiction research.

The risk of gaining weight may implicate behavioural traits and emotional states. We showed in rats that a risk-taking behavioural profile was associated both with increased preference for a high-fat (HF) diet and with increased motivational response to a palatable high-sucrose (HS) diet. Hypothalamic urocortin 2 expression was associated with the preference for the HF diet. We also tested the hypothesis that consumption of HS and HF diets separately or provided simultaneously (HFHS) affect anxiety-like behaviour and locomotion.

Furthermore, we showed that withdrawal from HFHS food affects diet-induced obesity-prone (OP) and obesity-resistant (OR) animals differently. OP animals had increased motivation (craving) for HS food pellets as measured by the operant self-administration technique during withdrawal. Dopamine receptor expression in the striatum differed between OP and OR animals both at access to HFHS and during withdrawal. This strongly implicates dopaminergic signaling in the OP phenotype.

In humans, food preferences may be monitored using questionnaires. We analyzed food preference data from parents of preschool children, and identified an inverse association of parental preference for high-fat high-protein food and overweight in children.

In conclusion, we have employed animal models previously used in the addiction field to identify molecular mechanisms related both to food preference and vulnerability to obesity, and to food craving associated with withdrawal from palatable food. These findings add to our current understanding of obesity.


Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2010. 93 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 526
Obesity, Reward, Food preferences, Dietary fats, Dietary carbohydrates, Anxiety, Dopamine, Craving, Operant self-administration
National Category
Pharmacology and Toxicology
Research subject
urn:nbn:se:uu:diva-119779 (URN)978-91-554-7734-9 (ISBN)
Public defence
2010-04-10, B42, BMC, Husargatan 3, Uppsala, 09:00 (English)
Available from: 2010-03-19 Created: 2010-03-01 Last updated: 2010-03-19Bibliographically approved

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