1 University of Guelph, Guelph, Canada.
2 The Rockefeller University, New York, USA.
J Psychopharmacol. 2018 Feb;32(2):215-222. doi: 10.1177/0269881117742116. Epub 2017 Dec 6.
Patients undergoing methadone maintenance treatment self-report enhanced preferences for, and excessive consumption of, foods rich in sugar. However, it is unclear whether these are direct pharmacological effects of methadone or the consequences of metabolic dysfunctions induced by addiction to illicit opiates. Hence, the current study in drug-naïve male Sprague-Dawley rats explored the effects of steady-state methadone delivered by osmotic mini-pumps (13 days; 0, 10, 30 mg/kg/day) on consumption of rat chow and a palatable, sweet, liquid high fructose corn syrup solution. Six days after the removal of the pumps, mRNA expression of genes involved in responses to stress and rewards were quantified: pro-opiomelanocortin in the hypothalamus, mu-opioid receptor in the nucleus accumbens, and dopamine D2 receptor in the dorsal striatum. Taste reactivity and locomotion tests were also performed throughout the study. It was found that methadone increased caloric intake from high fructose corn syrup and reduced caloric intake from chow, effects that could not be directly ascribed to changes in high fructose corn syrup taste reactivity or motor functions. However, the changes in caloric intake displayed significant tolerance, and mRNA expression analysis suggested that methadone attenuated the effect of high fructose corn syrup on pro-opiomelanocortin mRNA, and possibly on dopamine D2 receptor mRNA. These findings in rats suggest that the pharmacological effect of methadone, administered to achieve steady-state maintenance, may not be the primary cause of dietary alterations reported by patients maintained on methadone.
接受美沙酮维持治疗的患者自我报告称，他们更喜欢食用和过度食用富含糖分的食物。然而，目前尚不清楚这些是美沙酮的直接药理学作用，还是非法阿片类药物成瘾引起的代谢功能障碍的后果。因此，本研究在药物-naïve 雄性 Sprague-Dawley 大鼠中探索了通过渗透微型泵（13 天；0、10、30mg/kg/天）给予稳定状态的美沙酮对大鼠饲料和美味、甜、高果糖玉米糖浆溶液的消耗的影响。在移除泵后的六天，定量了参与应激和奖励反应的基因的 mRNA 表达：下丘脑的 pro-opiomelanocortin、伏隔核中的 mu 阿片受体和背侧纹状体中的多巴胺 D2 受体。在整个研究过程中还进行了味觉反应和运动测试。研究发现，美沙酮增加了对高果糖玉米糖浆的热量摄入，减少了对饲料的热量摄入，这些影响不能直接归因于高果糖玉米糖浆味觉反应或运动功能的变化。然而，热量摄入的变化表现出明显的耐受性，mRNA 表达分析表明，美沙酮减弱了高果糖玉米糖浆对 pro-opiomelanocortin mRNA 的影响，可能对多巴胺 D2 受体 mRNA 也有影响。这些在大鼠中的发现表明，给予稳定维持的美沙酮的药理学作用可能不是接受美沙酮维持治疗的患者报告的饮食改变的主要原因。
