Nina M. Beltran , Leslie L. Sullivan , Gabriela M. Naime , Vanessa Minervini , Katherine M. Serafine
{"title":"Eating a high fat/high carbohydrate diet enhances morphine tolerance, while eating a ketogenic diet mitigates morphine withdrawal in male rats","authors":"Nina M. Beltran , Leslie L. Sullivan , Gabriela M. Naime , Vanessa Minervini , Katherine M. Serafine","doi":"10.1016/j.ejphar.2025.177709","DOIUrl":null,"url":null,"abstract":"<div><div>Obesity is associated with greater prescription rates of pain-relieving drugs (i.e., opioids). However, it is not known if opioid sensitivity is altered by diet, in particular with regard to fat and carbohydrate consumption. While eating a high fat/high carbohydrate diet leads to weight gain, a high fat/low carbohydrate diet (i.e., a ketogenic diet) leads to weight loss. In this report, male Sprague-Dawley rats (<em>n</em> = 7–8/dietary group) ate either a standard, high fat/high carbohydrate, or ketogenic diet. Morphine-induced antinociception was evaluated using the warm water tail withdrawal procedure following saline or cumulative doses of morphine (0.32–56 mg/kg; i.p.). After acute morphine testing, rats were administered morphine twice-daily, increasing in quarter log doses every 3 days (3.2–56 mg/kg; i.p) for 19 days to induce dependence and evaluate tolerance. Next, naltrexone-precipitated withdrawal was evaluated. Based on previous data, it was hypothesized that the magnitude of tolerance would be greater from eating a high fat/high carbohydrate diet, while withdrawal would be less severe for rats eating a ketogenic diet. Antinociception induced by acute doses of morphine was comparable among groups, regardless of diet. Further, rats in all groups developed tolerance to morphine; however, the magnitude of tolerance was greater for rats eating the high fat/high carbohydrate diet as compared to those eating a ketogenic diet. Rats eating a ketogenic diet displayed less severe withdrawal than rats in other groups. These results suggest that dietary intake can impact morphine sensitivity in ways that might be relevant for chronic pain management and opioid use disorder.</div></div>","PeriodicalId":12004,"journal":{"name":"European journal of pharmacology","volume":"1000 ","pages":"Article 177709"},"PeriodicalIF":4.2000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European journal of pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0014299925004637","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Obesity is associated with greater prescription rates of pain-relieving drugs (i.e., opioids). However, it is not known if opioid sensitivity is altered by diet, in particular with regard to fat and carbohydrate consumption. While eating a high fat/high carbohydrate diet leads to weight gain, a high fat/low carbohydrate diet (i.e., a ketogenic diet) leads to weight loss. In this report, male Sprague-Dawley rats (n = 7–8/dietary group) ate either a standard, high fat/high carbohydrate, or ketogenic diet. Morphine-induced antinociception was evaluated using the warm water tail withdrawal procedure following saline or cumulative doses of morphine (0.32–56 mg/kg; i.p.). After acute morphine testing, rats were administered morphine twice-daily, increasing in quarter log doses every 3 days (3.2–56 mg/kg; i.p) for 19 days to induce dependence and evaluate tolerance. Next, naltrexone-precipitated withdrawal was evaluated. Based on previous data, it was hypothesized that the magnitude of tolerance would be greater from eating a high fat/high carbohydrate diet, while withdrawal would be less severe for rats eating a ketogenic diet. Antinociception induced by acute doses of morphine was comparable among groups, regardless of diet. Further, rats in all groups developed tolerance to morphine; however, the magnitude of tolerance was greater for rats eating the high fat/high carbohydrate diet as compared to those eating a ketogenic diet. Rats eating a ketogenic diet displayed less severe withdrawal than rats in other groups. These results suggest that dietary intake can impact morphine sensitivity in ways that might be relevant for chronic pain management and opioid use disorder.
期刊介绍:
The European Journal of Pharmacology publishes research papers covering all aspects of experimental pharmacology with focus on the mechanism of action of structurally identified compounds affecting biological systems.
The scope includes:
Behavioural pharmacology
Neuropharmacology and analgesia
Cardiovascular pharmacology
Pulmonary, gastrointestinal and urogenital pharmacology
Endocrine pharmacology
Immunopharmacology and inflammation
Molecular and cellular pharmacology
Regenerative pharmacology
Biologicals and biotherapeutics
Translational pharmacology
Nutriceutical pharmacology.