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Rat Model of Binge-eating Disorder

Rat Model of Binge-eating Disorder

 

Binge-eating disorder has recently been recognised to be a distinct psychiatric condition (DSM-5, May 2013). It affects approximately 2% of the adult European population and is characterised by recurring bouts of intense hyperphagia, usually of highly palatable ‘junk’ food. Binge-eating episodes are often accompanied by intense anxiety and guilt and in the period following these events, compensatory reductions in food intake may occur.

We have recently established a rat model of binge-eating disorder which exploits chocolate as a hedonistic food to stimulate binge-eating.

Key characteristics of our rat model of binge-eating disorder are:-

•   All rats are given free access to standard rat diet and presented with either an empty feeding jar (control animals) or with the chocolate diet for a limited period (2 h) on an irregular access schedule so that the animals do not know which days will be ‘binge days’.

  After 3-4 weeks of this regime, robust binge-eating develops. For example, during a 2 h ‘binge’, animals typically consume 140-160 kJ with a daily total intake of 300-350 kJ. In comparison, the control group eat less than 30 kJ over the 2 h period and approximately 240 kJ over 24 h.

•   Compensatory decreases in standard diet intake occur in the hours following binge-eating.

•   Body weights are unchanged (mirroring binge-eating disorder without associated obesity).

 

Development of Binge-eating in Rats

 

Effect of Chocolate Binge-eating on Body Weight in Rats

 

Our rodent model of binge-eating disorder has been validated by a range of drugs including lisdexamfetamine and nalmefene. Lisdexamfetamine is only drug approved by the FDA to treat adults with moderate to severe binge-eating disorder. Nalmefene is a μ-opioid receptor antagonist. The clinical potential of μ-opioid receptor antagonists as treatments for binge-eating disorder has recently been reported (Ziauddeen et al. 2013 [PudMed]).

Lisdexamfetamine and nalmefene selectively reduced chocolate bingeing without decreasing intake of standard rat chow. 

 

Effect of Lisdexamfetamine and Nalmefene on Chocolate and Chow Intake During a 2 h Binge Episode

 

 

Modelling compulsivity in binge-eating rats


Binge-eating disorder is characterised by repeated episodes of compulsive, excessive consumption of palatable food. As compulsivity is a key component in the psychopathology of binge-eating disorder, we have developed and validated a new behavioural test to evaluate compulsive/perseverative behaviour in binge-eating rats. 

In the food-associated conflict test, rats are trained to binge-eat as described above and then tested in two-chambered shuttle-boxes. Entry into a chamber containing chocolate leads to presentation of conditioned stimuli (light/tone) followed 10 sec later by mild foot-shock. Binge-eating rats develop compulsive consumption of chocolate that is resistant to the mildly aversive foot-shock compared to the control group ie compulsive/perseverative responding for chocolate. 

 

Compulsive/Perseverative Responding for Chocolate in Binge-eating Rats

 

The food-associated conflict test has been validated using lisdexamfetamine. The drug reduced the compulsive and perseverative behaviours of binge-eating rats (see Hutson et al. 2015a). The model can therefore be used to evaluate the effects of new drugs on the compulsivity component of binge-eating disorder psychopathology.

 

Modelling impulsivity in binge-eating rats


Impulsivity and loss of inhibitory control are important factors in binge-eating disorder. Subjects with binge-eating disorder display enhanced delay discounting, ie they will choose smaller, immediate rewards rather than wait for a larger, delayed reward. We have developed a delay discounting model to evaluate impulsivity and intolerance of delayed reward in binge-eating rats given irregular, limited access to chocolate. Binge-eating rats are trained to lever press for chocolate pellets in a two-lever operant chamber. One lever delivers a small immediate reward and the other lever a larger but delayed food reward. Binge-eating rats show a significant reduction in preference for the larger delayed reward compared to the control group ie they show lack of tolerance to delay for the larger chocolate reward. This intolerance of delayed reward develops over time with the number of binge-eating sessions and is characteristic of impulsive behaviour.

Delay Discounting Rodent Model of Impulsivity

 

The delay discounting model has been validated using lisdexamfetamine (see Hutson et al. 2015b). Thus, lisdexamfetamine prevented the impulsive responding of binge-eating rats for chocolate (ie their preference for a small, immediate reward rather than the larger, delayed reward). These results demonstrate that lisdexamfetamine increased inhibitory control in binge-eating rats given access to chocolate.

The delay discounting model can now be used to assess the effects of novel drugs on impulsivity in normal and binge-eating rats.

Please contact us for further information about our rodent model of binge-eating disorder, the food-associated conflict test and the delay discounting model.

 

Posters


Cheetham et al. 2014. Binge-eating behaviour produces alterations in dopaminergic neurochemistry in the brains of rats. Program No. 233.04. Presented at the Society for Neuroscience Meeting, Washington, DC, USA, 15th-19th November 2014.

 

Heal et al. 2014. Binge-eating behaviour in rats induces changes in dopamine and opioid receptor binding in the brain. Poster No. M12. Presented at the 53rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP), Phoenix, Arizona, USA, 7th-11th December 2014.

 

Hutson et al. 2014. Lisdexamfetamine-induced suppression of binge-eating in rats is attenuated by the α1-adrenoceptor antagonist, prazosin. Poster No. W187. Presented at the 53rd Annual Meeting of the American College of Neuropsychopharmacology (ACNP), Phoenix, Arizona, USA, 7th-11th December 2014.

 

Hutson et al. 2015a. Preclinical evidence showing that lisdexamfetamine (LDX) prevents compulsive and perseverative behaviour associated with binge-eating. Poster Session II, No. W56. Presented at the Annual Meeting of the American Society of Clinical Psychopharmacology (ASCP), Miami, Florida, USA, 22nd-25th June 2015.

 

Hutson et al. 2015b. Preclinical evidence to demonstrate that lisdexamfetamine prevents impulsivity in binge eating. Poster No. M46. Presented at the 54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP), The Diplomat Resort & Spa, Hollywood, Florida, USA, 6th-10th December 2015.

 

Tarazi et al. 2015. Reduced expression of GAD65/67 mRNA and dopamine Dand Dreceptors in binge-eating rats. Poster No. M48. Presented at the 54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP), The Diplomat Resort & Spa, Hollywood, Florida, USA, 6th-10th December, 2015.

 

Vickers et al. 2013. Effect of lisdexamfetamine in a rat model of binge-eating disorder. Program No. 236.03. Presented at the Society for Neuroscience Meeting, San Diego, California, USA, 9th-13th November 2013.

 

Vickers et al. 2015. Binge-eating rats show marked impulsivity in a delay discounting test. Program No. 723.09. Presented at the Society for Neuroscience Meeting, Chicago, Illinois, USA, 17th-21st October 2015. 

 

Manuscripts


Heal et al. 2016. Lisdexamfetamine reduces the compulsive and perseverative behaviour of binge-eating rats in a novel food reward/punished responding conflict model. J Psychopharmacol. 30: 662-675. [PubMed]

 

Heal et al. 2017. Dopamine and μ-opioid receptor dysregulation in the brains of binge-eating female rats - possible relevance in the psychopathology and treatment of binge-eating disorder. J. Psychopharmacol. 2017 Apr 1. doi: 10.1177/0269881117699607. [Epub ahead of print] [PubMed]

 

Vickers et al. 2015. Effects of lisdexamfetamine in a rat model of binge-eating. J Psychopharmacol. 29: 1290-1307. [PubMed]

 

Vickers et al. 2017. Investigation of impulsivity in binge-eating rats in a delay-discounting task and its prevention by the d-amphetamine prodrug, lisdexamfetamine. J Psychopharmacol. 2017 Feb 1. doi: 10.1177/0269881117691672. [Epub ahead of print] [PubMed]