Beltran Nina M, Sullivan Leslie L, Naime Gabriela M, Minervini Vanessa, Serafine Katherine M
Department of Psychology, The University of Texas at El Paso, El Paso, TX, USA.
Department of Psychological Science, Creighton University, Omaha, NE, USA.
Eur J Pharmacol. 2025 Aug 5;1000:177709. doi: 10.1016/j.ejphar.2025.177709. Epub 2025 May 8.
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.
肥胖与更高的止痛药物（即阿片类药物）处方率相关。然而，尚不清楚饮食是否会改变阿片类药物的敏感性，特别是在脂肪和碳水化合物摄入方面。虽然高脂/高碳水化合物饮食会导致体重增加，但高脂/低碳水化合物饮食（即生酮饮食）会导致体重减轻。在本报告中，雄性Sprague-Dawley大鼠（每组n = 7-8只）分别食用标准饮食、高脂/高碳水化合物饮食或生酮饮食。使用温水甩尾程序在给予生理盐水或累积剂量的吗啡（0.32-56 mg/kg；腹腔注射）后评估吗啡诱导的抗伤害感受。急性吗啡测试后，大鼠每天接受两次吗啡注射，每3天以四分之一对数剂量递增（3.2-56 mg/kg；腹腔注射），持续19天以诱导依赖性并评估耐受性。接下来，评估纳曲酮诱发的戒断反应。根据先前的数据，推测高脂/高碳水化合物饮食组的耐受性程度会更高，而生酮饮食组大鼠的戒断反应会较轻。无论饮食如何，急性剂量吗啡诱导的抗伤害感受在各组之间相当。此外，所有组的大鼠都对吗啡产生了耐受性；然而，与食用生酮饮食的大鼠相比，食用高脂/高碳水化合物饮食的大鼠耐受性程度更高。食用生酮饮食的大鼠比其他组的大鼠表现出较轻的戒断反应。这些结果表明，饮食摄入可能会以与慢性疼痛管理和阿片类药物使用障碍相关的方式影响吗啡敏感性。
