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

Abstract

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

Gut Microbiome in Anesthesiology and Pain Medicine

“…57 Moreover, after chronic treatment with oxycodone, the changes in the intestinal microbiome of mice persisted even after treatment was discontinued. 58 Interestingly, the host response to morphine is dependent on the gut microbiome: in a mouse model of morphine tolerance, germ-free mice and antibiotic-treated mice were less prone to developing opioid tolerance than were naïve mice. 59 Opioid tolerance was associated with the depletion of two bacterial groups: bifidobacteria and Lactobacillaeae.…”

“…57 Moreover, after chronic treatment with oxycodone, the changes in the intestinal microbiome of mice persisted even after treatment was discontinued. 58…”

Intravenous fentanyl self-administration in male and female C57BL/6J and DBA/2J mice

“…Viability of intravenous fentanyl self-administration in the mouse. Drinking and vapor selfadministration of fentanyl in mice [28][29][30][31] , intravenous self-administration of remifentanil in mice [32][33][34][35] , and intravenous self-administration of fentanyl in rats 13,[36][37][38] have all been described in the literature. Together, these studies have begun to uncover the biological mechanisms driving fentanyl addiction.…”

Omega-3 gantz-azidoen propietate onuragarriak zenbait egoera klinikotan

“…Areago, arrain olio gehigarriaren bidez diabetesa pairatzen duten pazienteek injektatu beharreko intsulina kantitatea baxuagoa izatea lortu da [91]. Azken urteetan omega-3-en baliagarritasuna opioide menpekotasunaren aurkako tratamenduan osagarri gisa aztertzen ari da, eta orain arte emaitza itxaropentsuak lortu dira [92]. Horregatik guztiagatik omega-3 GAk, epe luzera, hainbat gaixotasuni aurrea hartzeko edo halakoak tratatzeko etorkizun handiko gehigarria bilakatzen ari dira; dietaren bidez har ditzakegun propietate osagarri eta sendagarriko mantenugaiak baitira, edonoren eskura daudenak.…”