4.5 Article

N-acetylcysteine reduces addiction-like behaviour towards high-fat high-sugar food in diet-induced obese rats

Journal

EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 54, Issue 3, Pages 4877-4887

Publisher

WILEY
DOI: 10.1111/ejn.15321

Keywords

compulsive eating; diet-induced obesity; high-fat high-sugar diet; N-acetylcysteine; Sprague-Dawley

Categories

Funding

  1. Australian Research Council [1107144, 190101244]
  2. University of Melbourne
  3. National Health and Medical Research Council [110892, 1116930, 1166123, 1178482]
  4. National Health and Medical Research Council of Australia [1166123, 1178482] Funding Source: NHMRC

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Research suggests that NAC treatment can reduce addiction-like behavior towards food in rats, supporting its potential use in treating compulsive overeating.
Compulsive forms of eating displayed by some obese individuals share similarities with compulsive drug-taking behaviour, a hallmark feature of substance use disorder. This raises the possibility that drug addiction treatments may show utility in the treatment of compulsive overeating. N-Acetylcysteine (NAC) is a cysteine pro-drug which has experienced some success in clinical trials, reducing cocaine, marijuana and cigarette use, as well as compulsive behaviours such as gambling and trichotillomania. We assessed the impact of NAC on addiction-like behaviour towards highly palatable food in a rat model of diet-induced obesity. Adult male Sprague-Dawley rats were placed on a high-fat high-sugar diet for 8 weeks and then assigned to diet-induced obesity-prone (DIO) or diet-induced obesity-resistant (DR) groups based on weight gain. DIO and DR rats were subjected to an operant conditioning paradigm whereby rats could lever press for high-fat high-sugar food pellets. This alternated with periods of signalled reward unavailability. Before treatment DIO rats ate more in their home cage, earned more food pellets in operant sessions, and responded more during periods that signalled reward unavailability (suggestive of compulsive-like food seeking) compared with DR rats. This persistent responding in the absence of reward displayed by DIO rats was ameliorated by daily injections of NAC (100 mg/kg, i.p.) for 14 days. By the end of the treatment period, lever-pressing by NAC-treated DIO rats resembled that of DR rats. These findings suggest that NAC reduces addiction-like behaviour towards food in rats and supports the potential use of this compound in compulsive overeating.

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