Bulimia nervosa and binge eating disorder ("binge eating disorders") are serious public health problems, in part because people with these disorders tend also to suffer other medical complications, such as obesity and depression. Recently, animal models of binge eating have been developed, in which rats are provided intermittent access to sweet and/or high fat food. As consumption of this food escalates over several weeks of access, neurochemical changes in the nucleus accumbens (NAc) are observed, including increases in expression of opioid receptors. Pilot experiments show that injection of a broad-spectrum opioid receptor antagonist into the NAc has more pronounced effects on sweet/fat liquid consumption in binge eating than in control rats. These results suggest that binge eating could be due, at least in part, to upregulation of opioidergic neurotransmission in the NAc. To test this hypothesis, we will first determine which of three opioid receptors (mu, delta and kappa) in the NAc contributes to consumption of palatable liquid, and whether these contributions are different in binge eating and control rats. We will also determine whether these contributions are specific to the core or shell regions of the NAc. In addition, we will determine whether encoding of palatability by NAc neurons differs from controls in binge eating rats. Finally, we will test the hypotheses that endogenous opioids contribute to palatability encoding by NAc neurons, and that this contribution is different in binge eating vs control animals. Our goal is to elucidate the neural mechanisms that underlie binge eating, so that pharmaceutical treatments for binge eating disorders can be developed that specifically target these mechanisms. Because the same neural circuits are involved in drug addiction, our studies will also contribute towards understanding the neural mechanisms of addiction, and of reward-seeking behavior in general.

Public Health Relevance

Approximately 5% of the American population suffers, during at least part of adult life, from binge eating disorder or bulimia nervosa (binge eating disorders);these are serious public health problems because of the associated medical complications such as depression and obesity. The research proposed here will use an animal model of binge eating to help us understand how brain circuits that are critical for reward-seeking and feeding control these behaviors, and how circuit activity changes to produce binge eating. Identifying specific neural mechanisms responsible for binge eating will potentially stimulate the development of pharmacological interventions that specifically target these mechanisms to treat binge eating disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH092757-02
Application #
8411967
Study Section
Neurobiology of Motivated Behavior Study Section (NMB)
Program Officer
Rossi, Andrew
Project Start
2012-01-15
Project End
2014-12-31
Budget Start
2013-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2013
Total Cost
$200,400
Indirect Cost
$80,400
Name
Albert Einstein College of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Morrison, Sara E; Nicola, Saleem M (2014) Neurons in the nucleus accumbens promote selection bias for nearer objects. J Neurosci 34:14147-62
McGinty, Vincent B; Lardeux, Sylvie; Taha, Sharif A et al. (2013) Invigoration of reward seeking by cue and proximity encoding in the nucleus accumbens. Neuron 78:910-22
Lardeux, Sylvie; Kim, James J; Nicola, Saleem M (2013) Intermittent access to sweet high-fat liquid induces increased palatability and motivation to consume in a rat model of binge consumption. Physiol Behav 114-115:21-31