Addiction-like Synaptic Impairments in Diet-Induced Obesity

Robyn Mary Brown, Yonatan Michael Kupchik, Sade Spencer, Constanza Garcia-Keller, David C. Spanswick, Andrew John Lawrence, Stephanie Elise Simonds, Danielle Joy Schwartz, Kelsey Ann Jordan, Thomas Clayton Jhou, Peter William Kalivas

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)797-806
Number of pages10
JournalBiological Psychiatry
Volume81
Issue number9
DOIs
Publication statusPublished - 1 May 2017

Keywords

  • Food addiction
  • Glutamate
  • Long-term depression
  • Nucleus accumbens
  • Obesity
  • Synaptic plasticity

Cite this

Brown, R. M., Michael Kupchik, Y., Spencer, S., Garcia-Keller, C., Spanswick, D. C., Lawrence, A. J., ... William Kalivas, P. (2017). Addiction-like Synaptic Impairments in Diet-Induced Obesity. Biological Psychiatry, 81(9), 797-806. https://doi.org/10.1016/j.biopsych.2015.11.019
Brown, Robyn Mary ; Michael Kupchik, Yonatan ; Spencer, Sade ; Garcia-Keller, Constanza ; Spanswick, David C. ; Lawrence, Andrew John ; Simonds, Stephanie Elise ; Joy Schwartz, Danielle ; Ann Jordan, Kelsey ; Clayton Jhou, Thomas ; William Kalivas, Peter. / Addiction-like Synaptic Impairments in Diet-Induced Obesity. In: Biological Psychiatry. 2017 ; Vol. 81, No. 9. pp. 797-806.
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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.",
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Brown, RM, Michael Kupchik, Y, Spencer, S, Garcia-Keller, C, Spanswick, DC, Lawrence, AJ, Simonds, SE, Joy Schwartz, D, Ann Jordan, K, Clayton Jhou, T & William Kalivas, P 2017, 'Addiction-like Synaptic Impairments in Diet-Induced Obesity' Biological Psychiatry, vol. 81, no. 9, pp. 797-806. https://doi.org/10.1016/j.biopsych.2015.11.019

Addiction-like Synaptic Impairments in Diet-Induced Obesity. / Brown, Robyn Mary; Michael Kupchik, Yonatan; Spencer, Sade; Garcia-Keller, Constanza; Spanswick, David C.; Lawrence, Andrew John; Simonds, Stephanie Elise; Joy Schwartz, Danielle; Ann Jordan, Kelsey; Clayton Jhou, Thomas; William Kalivas, Peter.

In: Biological Psychiatry, Vol. 81, No. 9, 01.05.2017, p. 797-806.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Spencer, Sade

AU - Garcia-Keller, Constanza

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AU - Lawrence, Andrew John

AU - Simonds, Stephanie Elise

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AU - Ann Jordan, Kelsey

AU - Clayton Jhou, Thomas

AU - William Kalivas, Peter

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Brown RM, Michael Kupchik Y, Spencer S, Garcia-Keller C, Spanswick DC, Lawrence AJ et al. Addiction-like Synaptic Impairments in Diet-Induced Obesity. Biological Psychiatry. 2017 May 1;81(9):797-806. https://doi.org/10.1016/j.biopsych.2015.11.019