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

Department of Neuroscience Functional Pharmacology, Uppsala University, Uppsala, Sweden.
Psychopharmacology (Impact Factor: 3.88). 03/2009; 204(3):431-43. DOI: 10.1007/s00213-009-1474-y
Source: PubMed


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.

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    • "studies have indicated that sensitization of the reward pathway after chronic exposure to a high 358 fat, high sugar diet increased motivation for sucrose in adult male rats immediately after diet 359 withdrawal[44]. However, other studies focusing on drug addiction models have shown that a 360 hypofunctioning mesocorticolimbic dopamine system in the addicted brain promotes reward 361 seeking behavior[45,46]. "
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    • "These reward pathways are highly conserved across species and have been associated with altered responsiveness to reward (e.g., food) in obesity. Studies have demonstrated diminished responsiveness to perform food motivated behaviors and rewarding intracranial self-stimulation in obese rats (Volkow and Wise, 2005; la Fleur et al., 2007; Pickering et al., 2009; Johnson and Kenny, 2010) and reduced sensitivity to reward (measured by ratings of motivation and pleasure derived from engaging in rewarding behaviors) in obese humans (Davis et al., 2004). "
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    • "The animals withdrawn from the CAF diet behaved like CAF-fed animals in most of the behavioural tests except in the open field, where they showed a decrease in the time spent in the centre, thereby indicating increased anxiety compared to the CAF-fed animals. This is consistent with an interesting study of Pickering et al [53] who also found increased anxiety in the open field in diet-induced obese rats after 2 weeks of diet withdrawal. Animals receiving a high-fat high-sugar (HFHS) diet for 7 weeks were divided into obesity-prone and obesity-resistant groups based on the relative weight gain and tested 2 weeks after withdrawal. "
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