Effect of high-fat diet-induced obesity on the efficacy of food and drug reinforcers.

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Restricting access to food in rodents is known to enhance the efficacy of reinforcers such as food, brain self-stimulation, and drugs of abuse (e.g., cocaine, amphetamine) in a number of procedures including operant self-administration and conditioned place preference. Food restriction reduces body weight, body adiposity and plasma leptin, a hormone recently found to modulate the mesolimbic dopamine system. In contrast, placing rodents on a high-fat, calorically dense diet induces hyperphagia and sustained gains in body weight, adiposity and plasma leptin. Here, we test the prediction that high-fat diet (HFD)- induced obesity will result in reduced sensitivity to reinforcing stimuli. We find that male and female rats maintained on HFD display reduced operant responding for a variety of food reinforcers, including sucrose pellets, peanut oil, and a liquid sucrose solution. HFD is strongly preferred over low fat diets and switching from a preferred to a non-preferred reinforcer strongly attenuates responding, a phenomenon known as a negative contrast effect. To assess the possibility that our observed reduction in operant responding represents a negative contrast between HFD and the selected food stimuli, we also assessed operant responding in a group of animals fed the HFD in an amount calorically matched to a group consuming the control diet. We also assessed responding in animals selectively bred for their susceptibility or resistance to obesity when consuming HFD. Finally, the effect of HFD-induced obesity on a non-food reinforcer was evaluated by assessing the ability of amphetamine to condition a place preference in HFD- and chow-fed rats.