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Neuropharmacology. 2014 Jan;76 Pt B:395-406. doi: 10.1016/j.neuropharm.2013.04.030. Epub 2013 May 6.

The use of the reinstatement model to study relapse to palatable food seeking during dieting.

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Behavioral Neuroscience Branch, Intramural Research Program, NIDA/NIH, Baltimore, MD, USA. Electronic address:


Excessive consumption of unhealthy foods is a major public health problem. While many people attempt to control their food intake through dieting, many relapse to unhealthy eating habits within a few months. We have begun to study this clinical condition in rats by adapting the reinstatement model, which has been used extensively to study relapse to drug seeking. In our adaptation of the relapse model, reinstatement of palatable food seeking by exposure to food-pellet priming, food-associated cues, or stress is assessed in food-restricted (to mimic dieting) rats after operant food-pellet self-administration training and subsequent extinction of the food-reinforced responding. In this review, we first outline the clinical problem and discuss a recent study in which we assessed the predictive validity of the reinstatement model for studying relapse to food seeking during dieting by using the anorexigenic drug fenfluramine. Next, we summarize results from our initial studies on the role of several stress- and feeding-related peptides (corticotropin-releasing factor, hypocretin, melanin-concentrating hormone, peptide YY3-36) in reinstatement of palatable food seeking. We then present results from our studies on the role of dopamine and medial prefrontal cortex in stress-induced reinstatement of food seeking. We conclude by discussing potential clinical implications. We offer two main conclusions: (1) the food reinstatement model is a simple, reliable, and valid model to study mechanisms of relapse to palatable food seeking during dieting, and to identify medications to prevent this relapse; (2) mechanisms of relapse to food seeking are often dissociable from mechanisms of ongoing food intake. This article is part of a Special Issue entitled 'NIDA 40th Anniversary Issue'.


Dieting; Food; Priming; Reinstatement; Relapse; Self-administration; Stress; cue

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