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Addiction-like Synaptic Impairments in Diet-Induced Obesity

Published:December 02, 2015DOI:https://doi.org/10.1016/j.biopsych.2015.11.019

      Abstract

      Background

      There is increasing evidence that the pathological overeating underlying some forms of obesity is compulsive in nature and therefore contains elements of an addictive disorder. However, direct physiological evidence linking obesity to synaptic plasticity akin to that occurring in addiction is lacking. We sought to establish whether the propensity to diet-induced obesity (DIO) is associated with addictive-like behavior, as well as synaptic impairments in the nucleus accumbens core considered hallmarks of addiction.

      Methods

      Sprague Dawley rats were allowed free access to a palatable diet for 8 weeks then separated by weight gain into DIO-prone and DIO-resistant subgroups. Access to palatable food was then restricted to daily operant self-administration sessions using fixed ratio 1, 3, and 5 and progressive ratio schedules. Subsequently, nucleus accumbens brain slices were prepared, and we tested for changes in the ratio between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate currents and the ability to exhibit long-term depression.

      Results

      We found that propensity to develop DIO is linked to deficits in the ability to induce long-term depression in the nucleus accumbens, as well as increased potentiation at these synapses as measured by AMPA/N-methyl-D-aspartate currents. Consistent with these impairments, we observed addictive-like behavior in DIO-prone rats, including 1) heightened motivation for palatable food; 2) excessive intake; and 3) increased food seeking when food was unavailable.

      Conclusions

      Our results show overlap between the propensity for DIO and the synaptic changes associated with facets of addictive behavior, supporting partial coincident neurological underpinnings for compulsive overeating and drug addiction.

      Keywords

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      Linked Article

      • New Evidence Linking Obesity and Food Addiction
        Biological PsychiatryVol. 81Issue 9
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          Obesity rates have skyrocketed over the past few decades. In the United States, approximately 35% of adults are now considered obese, with more than 60% categorized as overweight (1). The health consequences of obesity are substantial. Obesity increases the risk of developing several debilitating conditions, such as diabetes, heart disease, stroke, and mental illness. Because the global obesity epidemic is generally believed to be caused by excessive caloric intake, there has been increasing interest in understanding the neurobiological mechanisms contributing to overeating, defined as continued eating in the absence of metabolic necessity leading to weight gain.
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