Archive | 2019

Dietary Supplementation with Omega-3 Polyunsaturated Fatty Acids Reduces Opioid-1 Seeking Behaviors and Alters the Gut Microbiome 2 3

 
 
 
 
 
 
 
 
 
 
 
 
 
 

Abstract


Opioids are highly addictive substances with a relapse rate of over 90%. While preclinical 22 models of chronic opioid exposure exist for studying opioid dependence, none recapitulate the relapses 23 observed in human opioid addiction. The mechanisms associated with opioid dependence, the 24 accompanying withdrawal symptoms and the relapses that are often observed months or years after opioid 25 dependence are poorly understood. Therefore, we developed a novel model of chronic opioid exposure 26 whereby the level of administration is self-directed with periods of behavior acquisition, maintenance and 27 then extinction alternating with reinstatement. This profile arguably mirrors that seen in humans, with 28 initial opioid use followed by alternating periods of abstinence and relapse. Recent evidence suggests that 29 dietary interventions that reduce inflammation, including omega-3 fatty acids such as docosahexaenoic 30 acid (DHA), may reduce substance misuse liability. Using the self-directed intake model, we characterize 31 the observed profile of opioid use and demonstrate that a diet enriched in polyunsaturated fat acids 32 (PUFAs) ameliorates oxycodone-seeking behaviors in the absence of drug availability and reduces anxiety. 33 Guided by the major role gut microbiota have on brain function, neuropathology, and anxiety, we profile 34 the microbiome composition and the effects of chronic opioid exposure and DHA supplementation. We 35 demonstrate that withdrawal of opioids led to a significant depletion in specific microbiota genera whereas 36 DHA supplementation increased microbial richness, phylogenetic diversity, and evenness. Lastly, we 37 examined the activation state of microglia in the striatum and found that DHA supplementation reduced 38 the basal activation state of microglia. These preclinical data suggest that a diet enriched in PUFAs could 39 be used as a treatment to alleviate anxiety induced opioid-seeking behavior and relapse in human opioid 40 addiction. 41 42

Volume None
Pages None
DOI 10.20944/preprints201907.0247.v1
Language English
Journal None

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