Dietary supplementation with fish oil prevents high fat diet-induced enhancement of sensitivity to the locomotor stimulating effects of cocaine in adolescent female rats

Drug Alcohol Depend. 2016 Aug 1:165:45-52. doi: 10.1016/j.drugalcdep.2016.05.013. Epub 2016 May 24.


Background: Eating a diet high in fat can lead to obesity, chronic metabolic disease, and increased inflammation in both the central and peripheral nervous systems. Dietary supplements that are high in omega-3 polyunsaturated fatty acids can reduce or prevent these negative health consequences in rats. Eating high fat chow also increases the sensitivity of rats to behavioral effects of drugs acting on dopamine systems (e.g., cocaine), and this effect is greatest in adolescent females.

Methods: The present experiment tested the hypothesis that dietary supplementation with fish oil prevents high fat chow induced increases in sensitivity to cocaine in adolescent female rats. Female Sprague-Dawley rats (post-natal day 25-27) ate standard laboratory chow (5.7% fat), high fat chow (34.4% fat), or high fat chow supplemented with fish oil (20% w/w). Cocaine dose dependently (1-17.8mg/kg) increased locomotion and induced sensitization across 6 weeks of once-weekly testing in all rats; however, these effects were greatest in rats eating high fat chow.

Results: Dietary supplementation with fish oil prevented enhanced locomotion and sensitization in rats eating high fat chow. There were no differences in inflammatory markers in plasma or the hypothalamus among dietary conditions.

Conclusions: These results demonstrate that dietary supplementation with fish oil can prevent high fat diet-induced sensitization to cocaine, but they fail to support the view that these effects are due to changes in proinflammatory cytokines. These data add to a growing literature on the relationship between diet and drug abuse and extend the potential health benefits of fish oil to stimulant drug abuse prevention.

Keywords: Cocaine; Dopamine; Fish oil; High-fat chow; Rat; Sensitization.

MeSH terms

  • Animals
  • Central Nervous System Sensitization / drug effects*
  • Cocaine / pharmacology*
  • Diet, High-Fat / adverse effects*
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Fish Oils / pharmacology*
  • Hypothalamus / metabolism
  • Inflammation Mediators / blood
  • Inflammation Mediators / metabolism
  • Locomotion / drug effects*
  • Rats
  • Rats, Sprague-Dawley


  • Fish Oils
  • Inflammation Mediators
  • Cocaine