Elsevier

Biological Psychiatry

Volume 67, Issue 9, 1 May 2010, Pages 880-886
Biological Psychiatry

Archival Report
Ghrelin Increases the Rewarding Value of High-Fat Diet in an Orexin-Dependent Manner

https://doi.org/10.1016/j.biopsych.2009.10.030Get rights and content

Background

Ghrelin is a potent orexigenic hormone that likely impacts eating via several mechanisms. Here, we hypothesized that ghrelin can regulate extra homeostatic, hedonic aspects of eating behavior.

Methods

In the current study, we assessed the effects of different pharmacological, physiological, and genetic models of increased ghrelin and/or ghrelin-signaling blockade on two classic behavioral tests of reward behavior: conditioned place preference (CPP) and operant conditioning.

Results

Using both CPP and operant conditioning, we found that ghrelin enhanced the rewarding value of high-fat diet (HFD) when administered to ad lib-fed mice. Conversely, wild-type mice treated with ghrelin receptor antagonist and ghrelin receptor-null mice both failed to show CPP to HFD normally observed under calorie restriction. Interestingly, neither pharmacologic nor genetic blockade of ghrelin signaling inhibited the body weight homeostasis-related, compensatory hyperphagia associated with chronic calorie restriction. Also, ghrelin's effects on HFD reward were blocked in orexin-deficient mice and wild-type mice treated with an orexin 1 receptor antagonist.

Conclusions

Our results demonstrate an obligatory role for ghrelin in certain rewarding aspects of eating that is separate from eating associated with body weight homeostasis and that requires the presence of intact orexin signaling.

Section snippets

Animals and Housing

Male mice were housed in a 12-hour light/dark cycle with regular chow (RC) (4 g% fat, diet #7001, Harlan-Teklad, Madison, Wisconsin), which provides 2.9 kcal/g of energy, and water available ad lib, except when indicated. All animal procedures were carried out in accordance with National Institutes of Health guidelines and University of Texas Southwestern Institutional Animal Care and Use Committee guidelines. Adult (8–10 weeks old) C57BL6/J mice were from Jackson Laboratory (Sacramento,

Results

To investigate a role for ghrelin in the rewarding properties of HFD, we adapted a version of the CPP task that is typically used in drug abuse studies. In this task, mice were conditioned to associate one chamber of the CPP apparatus with HFD and a second chamber with an equal calorie amount of RC. After a 12-day conditioning period (6 days on the HFD-paired side, alternating every other day with 6 days on the RC-paired side), mice were permitted free access to both chambers in the absence of

Discussion

The present study identifies a required role for ghrelin in mediating certain hedonic and motivational components of eating. Our results, together with the previous functional magnetic resonance imaging findings of ghrelin-induced increases in the neural response to food pictures within human brain regions implicated in encoding the incentive value of food cues, allow us to add food reward to a growing list of other reward behaviors, including cocaine seeking and alcohol reward, influenced by

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    Authors ML and JMZ contributed equally to this work.

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