Skip to main content
Log in

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

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Introduction

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.

Conclusion

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Alexander J, Chang GQ, Dourmashkin JT, Leibowitz SF (2006) Distinct phenotypes of obesity-prone AKR/J, DBA2J and C57BL/6 J mice compared to control strains. Int J Obes (Lond) 30:50–9

    Article  CAS  Google Scholar 

  • Anton RF, Moak DH, Latham P, Waid LR, Myrick H, Voronin K, Thevos A, Wang W, Woolson R (2005) Naltrexone combined with either cognitive behavioral or motivational enhancement therapy for alcohol dependence. J Clin Psychopharmacol 25:349–57

    Article  PubMed  CAS  Google Scholar 

  • Avena NM, Bocarsly ME, Rada P, Kim A, Hoebel BG (2008a) After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance. Physiol Behav 94:309–15

    Article  PubMed  CAS  Google Scholar 

  • Avena NM, Rada P, Hoebel BG (2008b) Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake. Neurosci Biobehav Rev 32:20–39

    Article  PubMed  CAS  Google Scholar 

  • Avena NM, Rada P, Hoebel BG (2008c) Underweight rats have enhanced dopamine release and blunted acetylcholine response in the nucleus accumbens while bingeing on sucrose. Neuroscience 156:865–71

    Article  PubMed  CAS  Google Scholar 

  • Bassareo V, De Luca MA, Di Chiara G (2002) Differential expression of motivational stimulus properties by dopamine in nucleus accumbens shell versus core and prefrontal cortex. J Neurosci 22:4709–19

    PubMed  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1997) Differential influence of associative and nonassociative learning mechanisms on the responsiveness of prefrontal and accumbal dopamine transmission to food stimuli in rats fed ad libitum. J Neurosci 17:851–61

    PubMed  CAS  Google Scholar 

  • Bassareo V, Di Chiara G (1999) Differential responsiveness of dopamine transmission to food-stimuli in nucleus accumbens shell/core compartments. Neuroscience 89:637–41

    Article  PubMed  CAS  Google Scholar 

  • Boggiano MM, Artiga AI, Pritchett CE, Chandler-Laney PC, Smith ML, Eldridge AJ (2007) High intake of palatable food predicts binge-eating independent of susceptibility to obesity: an animal model of lean vs obese binge-eating and obesity with and without binge-eating. Int J Obes (Lond) 31:1357–67

    Article  CAS  Google Scholar 

  • Buonopane A, Petrakis IL (2005) Pharmacotherapy of alcohol use disorders. Subst Use Misuse 40(2001–20):2043–8

    Google Scholar 

  • Colantuoni C, Rada P, McCarthy J, Patten C, Avena NM, Chadeayne A, Hoebel BG (2002) Evidence that intermittent, excessive sugar intake causes endogenous opioid dependence. Obes Res 10:478–88

    Article  PubMed  CAS  Google Scholar 

  • Collins S, Martin TL, Surwit RS, Robidoux J (2004) Genetic vulnerability to diet-induced obesity in the C57BL/6 J mouse: physiological and molecular characteristics. Physiol Behav 81:243–8

    Article  PubMed  CAS  Google Scholar 

  • Denenberg VH (1969) Open-field behavior in the rat: what does it mean? Ann N Y Acad Sci 159:852–9

    Article  PubMed  CAS  Google Scholar 

  • Eichler K, Zoller M, Steurer J, Bachmann LM (2007) Cognitive-behavioural treatment for weight loss in primary care: a prospective study. Swiss Med Wkly 137:489–95

    PubMed  Google Scholar 

  • Ferster CB, Skinner BF (1957) Schedules of Reinforcement. Appleton-Century-Crofts, Appleton-Century-Crofts

    Book  Google Scholar 

  • Galarce EM, Crombag HS, Holland PC (2007) Reinforcer-specificity of appetitive and consummatory behavior of rats after Pavlovian conditioning with food reinforcers. Physiol Behav 91:95–105

    Article  PubMed  CAS  Google Scholar 

  • Heilig M, Egli M (2006) Pharmacological treatment of alcohol dependence: target symptoms and target mechanisms. Pharmacol Ther 111:855–76

    Article  PubMed  CAS  Google Scholar 

  • Heyser CJ, Schulteis G, Koob GF (1997) Increased ethanol self-administration after a period of imposed ethanol deprivation in rats trained in a limited access paradigm. Alcohol Clin Exp Res 21:784–91

    PubMed  CAS  Google Scholar 

  • Hill AJ (2007) The psychology of food craving. Proc Nutr Soc 66:277–85

    Article  PubMed  Google Scholar 

  • Holter SM, Linthorst AC, Reul JM, Spanagel R (2000) Withdrawal symptoms in a long-term model of voluntary alcohol drinking in Wistar rats. Pharmacol Biochem Behav 66:143–51

    Article  PubMed  CAS  Google Scholar 

  • Katz RJ, Roth KA, Carroll BJ (1981) Acute and chronic stress effects on open field activity in the rat: implications for a model of depression. Neurosci Biobehav Rev 5:247–51

    Article  PubMed  CAS  Google Scholar 

  • la Fleur SE, Akana SF, Manalo SL, Dallman MF (2004) Interaction between corticosterone and insulin in obesity: regulation of lard intake and fat stores. Endocrinology 145:2174–85

    Article  PubMed  Google Scholar 

  • la Fleur SE, Vanderschuren LJ, Luijendijk MC, Kloeze BM, Tiesjema B, Adan RA (2007) A reciprocal interaction between food-motivated behavior and diet-induced obesity. Int J Obes (Lond) 31:1286–94

    Article  Google Scholar 

  • Leibowitz KL, Chang GQ, Pamy PS, Hill JO, Gayles EC, Leibowitz SF (2007) Weight gain model in prepubertal rats: prediction and phenotyping of obesity-prone animals at normal body weight. Int J Obes (Lond) 31:1210–21

    Article  CAS  Google Scholar 

  • Levin BE, Dunn-Meynell AA, Balkan B, Keesey RE (1997) Selective breeding for diet-induced obesity and resistance in Sprague-Dawley rats. Am J Physiol 273:R725–30

    PubMed  CAS  Google Scholar 

  • Markou A, Weiss F, Gold LH, Caine SB, Schulteis G, Koob GF (1993) Animal models of drug craving. Psychopharmacology (Berl) 112:163–82

    Article  CAS  Google Scholar 

  • McTigue KM, Harris R, Hemphill B, Lux L, Sutton S, Bunton AJ, Lohr KN (2003) Screening and interventions for obesity in adults: summary of the evidence for the U.S. Preventive Services Task Force. Ann Intern Med 139:933–49

    PubMed  Google Scholar 

  • Mierzejewski P, Koros E, Goldberg SR, Kostowski W, Stefanski R (2003) Intravenous self-administration of morphine and cocaine: a comparative study. Pol J Pharmacol 55:713–26

    PubMed  CAS  Google Scholar 

  • Moreira T, Cebers G, Cebere A, Wagner A, Liljequist S (2005) Extradural compression of the sensorimotor cortex delays the acquisition but not the recalling of a lever-pressing task in Wistar rats. Behav Brain Res 164:250–65

    Article  PubMed  Google Scholar 

  • Pecoraro N, Reyes F, Gomez F, Bhargava A, Dallman MF (2004) Chronic stress promotes palatable feeding, which reduces signs of stress: feedforward and feedback effects of chronic stress. Endocrinology 145:3754–62

    Article  PubMed  CAS  Google Scholar 

  • Pelchat ML (2002) Of human bondage: food craving, obsession, compulsion, and addiction. Physiol Behav 76:347–52

    Article  PubMed  CAS  Google Scholar 

  • Pickering C, Avesson L, Lindblom J, Liljequist S, Schioth HB (2007a) Identification of neurotransmitter receptor genes involved in alcohol self-administration in the rat prefrontal cortex, hippocampus and amygdala. Prog Neuropsychopharmacol Biol Psychiatry 31:53–64

    Article  PubMed  CAS  Google Scholar 

  • Pickering C, Liljequist S (2003) Cue-induced behavioural activation: a novel model of alcohol craving? Psychopharmacology (Berl) 168:307–13

    Article  CAS  Google Scholar 

  • Pickering C, Moreira T, Liljequist S (2007b) Delayed access to alcohol accelerates self-administration of alcohol on a progressive ratio schedule. Basic Clin Pharmacol Toxicol 100:109–14

    PubMed  CAS  Google Scholar 

  • Prut L, Belzung C (2003) The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharmacol 463:3–33

    Article  PubMed  CAS  Google Scholar 

  • Rada P, Avena NM, Hoebel BG (2005) Daily bingeing on sugar repeatedly releases dopamine in the accumbens shell. Neuroscience 134:737–44

    Article  PubMed  CAS  Google Scholar 

  • Richardson NR, Roberts DC (1996) Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66:1–11

    Article  PubMed  CAS  Google Scholar 

  • Schemmel R, Mickelsen O, Gill JL (1970) Dietary obesity in rats: body weight and body fat accretion in seven strains of rats. J Nutr 100:1041–8

    PubMed  CAS  Google Scholar 

  • Shepherd J, Harden A, Rees R, Brunton G, Garcia J, Oliver S, Oakley A (2006) Young people and healthy eating: a systematic review of research on barriers and facilitators. Health Educ Res 21:239–57

    Article  PubMed  CAS  Google Scholar 

  • Skinner BF (1938) The Behavior of Organisms: An Experimental Analysis. B F Skinner Foundation, B F Skinner Foundation

    Google Scholar 

  • Stafford D, LeSage MG, Glowa JR (1998) Progressive-ratio schedules of drug delivery in the analysis of drug self-administration: a review. Psychopharmacology (Berl) 139:169–84

    Article  CAS  Google Scholar 

  • Tiffany ST, Carter BL (1998) Is craving the source of compulsive drug use? J Psychopharmacol 12:23–30

    Article  PubMed  CAS  Google Scholar 

  • Tiffany ST, Conklin CA (2000) A cognitive processing model of alcohol craving and compulsive alcohol use. Addiction 95(Suppl 2):S145–53

    PubMed  Google Scholar 

  • Vanderschuren LJ, Everitt BJ (2005) Behavioral and neural mechanisms of compulsive drug seeking. Eur J Pharmacol 526:77–88

    Article  PubMed  CAS  Google Scholar 

  • Wang J, Alexander JT, Zheng P, Yu HJ, Dourmashkin J, Leibowitz SF (1998) Behavioral and endocrine traits of obesity-prone and obesity-resistant rats on macronutrient diets. Am J Physiol 274:E1057–66

    PubMed  CAS  Google Scholar 

  • Weiss F (2005) Neurobiology of craving, conditioned reward and relapse. Curr Opin Pharmacol 5:9–19

    Article  PubMed  CAS  Google Scholar 

  • Volkow ND, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8:555–60

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Jonas Lindblom for valuable discussions. The studies were supported by the Swedish Research Council, AFA insurance, Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, Åhlen Foundation and The Novo Nordisk Foundation. CP was supported by the Swedish Brain Foundation (Hjärnfonden).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chris Pickering.

Additional information

Chris Pickering and Johan Alsiö contributed equally to this manuscript.

CP and JA designed and performed the experiments and analysed the results. CP, JA, ALH and HBS wrote the manuscript.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Table 1

(DOC 20.8 KB)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pickering, C., Alsiö, J., Hulting, AL. et al. Withdrawal from free-choice high-fat high-sugar diet induces craving only in obesity-prone animals. Psychopharmacology 204, 431–443 (2009). https://doi.org/10.1007/s00213-009-1474-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1474-y

Keywords

Navigation