Addiction-like Synaptic Impairments in Diet-Induced Obesity. Biol Psychiatry 2017 May 01;81(9):797-806
Date
02/02/2016Pubmed ID
26826876Pubmed Central ID
PMC4889544DOI
10.1016/j.biopsych.2015.11.019Scopus ID
2-s2.0-84955572072 (requires institutional sign-in at Scopus site) 69 CitationsAbstract
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.
Author List
Brown RM, Kupchik YM, Spencer S, Garcia-Keller C, Spanswick DC, Lawrence AJ, Simonds SE, Schwartz DJ, Jordan KA, Jhou TC, Kalivas PWAuthor
Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBehavior, Addictive
Conditioning, Operant
Diet
Feeding Behavior
Glutamic Acid
Long-Term Synaptic Depression
Male
Neuronal Plasticity
Nucleus Accumbens
Obesity
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Receptors, N-Methyl-D-Aspartate