Iqbal Asif, Hamid Abdul, Ahmad Syed Muzzammil, Lutfy Kabirullah
Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA 91766-1854, USA.
Life (Basel). 2023 Feb 23;13(3):619. doi: 10.3390/life13030619.
Excessive high fat diet (HFD) consumption can induce food addiction, which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain areas are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in rewards elicited by palatable food. This study sought to investigate the involvement of MORs in HFD-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would alter the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used as an animal model of reward to determine if short-time (STC, 2 h) or long-time (LTC, 16 h) conditioning with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and their wildtype littermates of both sexes were tested for basal place preference on day 1 and then conditioned with an HFD in one chamber and a regular chow diet (RCD) in another chamber for 2 h on alternate days. Three sets of STC were used, followed by a set of LTC. Each set of conditioning consisted of two conditioning with RCD and two conditioning with HFD. Mice were tested for place preference after each set of STC and again after LTC. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and with saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in male but not female subjects. However, oxycodone conditioning elicited reward in both male and female mice of the HFD group but not the control group, showing that prior conditioning with HFD potentiated the rewarding action of oxycodone. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. Similarly, HFD-induced CPP was blunted in male MOR knockout mice, suggesting sexual dimorphism in this response.
过量食用高脂饮食（HFD）会引发食物成瘾，据信这涉及下丘脑与中脑边缘多巴胺能神经元之间的通讯，这些神经元起源于腹侧被盖区（VTA）并投射到伏隔核（NAc）。这些脑区富含阿片受体，这增加了这些受体，特别是μ阿片受体（MORs）参与美味食物引发的奖赏的可能性。本研究旨在调查MORs在HFD诱导的奖赏中的作用，以及在这种反应中雄性和雌性受试者之间是否存在差异。我们还评估了暴露于HFD是否会改变羟考酮（一种相对选择性的MOR激动剂）的奖赏作用。位置条件反射范式被用作奖赏的动物模型，以确定用HFD进行短期（STC，2小时）或长期（LTC，16小时）条件反射是否会诱导奖赏或改变羟考酮的奖赏作用。在第1天对雄性和雌性C57BL/6J小鼠以及MOR基因敲除小鼠及其野生型同窝小鼠进行基础位置偏好测试，然后隔天在一个隔室中用HFD进行条件反射，在另一个隔室中用常规饲料（RCD）进行条件反射，持续2小时。使用了三组STC，随后是一组LTC。每组条件反射包括两次用RCD进行的条件反射和两次用HFD进行的条件反射。在每组STC后以及LTC后对小鼠进行位置偏好测试。对照组在两个条件反射隔室中均用RCD进行条件反射。在最后一次位置偏好测试后，每天一次给小鼠注射羟考酮，并在与HFD配对的隔室中进行条件反射，在与RCD配对的隔室中注射生理盐水，持续一小时，以探究HFD是否会改变羟考酮奖赏的可能性。结果表明，HFD在雄性而非雌性受试者中诱导了条件性位置偏好（CPP）。然而，羟考酮条件反射在HFD组的雄性和雌性小鼠中均引发了奖赏，但在对照组中未引发，这表明先前用HFD进行条件反射增强了羟考酮的奖赏作用。后一种反应是通过MORs介导的，因为在MOR基因敲除小鼠中这种反应减弱了。同样，HFD诱导的CPP在雄性MOR基因敲除小鼠中减弱，表明这种反应存在性别差异。
