Access to high-fat diet results in increased sensitivity to the psychostimulant effects of MDPV in mice.

IF 3.6 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacological Reports Pub Date : 2025-04-01 Epub Date: 2025-01-27 DOI:10.1007/s43440-025-00701-0
Jakub Wojcieszak, Katarzyna Kuczyńska, Adrianna Leszczyńska, Eryk Naraziński, Maria Cichalewska-Studzińska
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引用次数: 0

Abstract

Background: The current study investigated the effects of high-fat diet on acute response to 3,4-methylenedioxypyrovalerone (MDPV) in mice. MDPV is a beta-cathinone derivative endowed with psychostimulant activity. Similarly to recreational substances, consumption of palatable food stimulates the mesolimbic dopaminergic system, resulting in neuroadaptive changes.

Methods: Adolescent C57BL/6N mice were fed either control diet (CD), 10% of kcal from fat, or high-fat diet (HFD), 60% of kcal from fat. After eight weeks, one group of HFD-fed mice had their diet changed to CD for an additional two weeks. Fasting glucose levels and glucose tolerance were measured to detect impairment in glucose metabolism. Subsequently, the mice were treated with either MDPV (1 mg/kg) or saline, and their locomotor activity was measured. Using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR), the expression of dopamine receptor D1 (Drd1), dopamine receptor D2 (Drd2), and FBJ osteosarcoma oncogene B (FosB) genes was measured in the striatum of mice.

Results: Feeding with HFD caused obesity and glucose intolerance in mice. Restriction of fat reduced body mass and reversed impairment of glucose metabolism. HFD-fed mice responded to MDPV with higher potency than CD-fed counterparts, with an increased incidence of stereotypies. A change of diet partially reversed this effect. Downregulation of Drd2 was observed in the mice that switched from HFD to CD, whereas treatment with MDPV caused upregulation of FosB only in the CD-fed mice.

Conclusions: Current results suggest that obesity may increase sensitivity to psychostimulant effects of MDPV and elevate the risk of addiction as mice fed with HFD responded to acute treatment with MDPV with higher potency and showed tolerance of FosB induction in response to the drug.

高脂肪饮食导致小鼠对MDPV精神兴奋作用的敏感性增加。
背景:本研究旨在研究高脂肪饮食对小鼠3,4-亚甲基二氧基戊烷酮(MDPV)急性反应的影响。MDPV是一种具有精神兴奋剂活性的-卡西酮衍生物。与娱乐性物质类似,食用美味食物会刺激中脑边缘多巴胺系统,导致神经适应性变化。方法:将青春期C57BL/6N小鼠分为对照组(CD)和高脂组(HFD),分别饲喂10%的热量来自脂肪和60%的热量来自脂肪。八周后,一组以hfd喂养的小鼠在另外两周内将饮食改为乳糜泻。测量空腹血糖水平和葡萄糖耐量以检测葡萄糖代谢的损害。随后,小鼠分别接受MDPV (1 mg/kg)或生理盐水治疗,并测量其运动活动。采用逆转录酶定量聚合酶链反应(RT-qPCR)技术,检测小鼠纹状体中多巴胺受体D1 (Drd1)、多巴胺受体D2 (Drd2)和FBJ骨肉瘤癌基因B (FosB)基因的表达。结果:HFD喂养引起小鼠肥胖和葡萄糖耐受不良。限制脂肪可以减少体重并逆转葡萄糖代谢的损害。hfd喂养的小鼠对MDPV的反应比cd喂养的小鼠更有效,刻板印象的发生率增加。饮食的改变部分地扭转了这种影响。在从HFD转换为CD的小鼠中观察到Drd2的下调,而用MDPV治疗仅在CD喂养的小鼠中引起FosB的上调。结论:目前的研究结果表明,肥胖可能会增加对MDPV精神兴奋作用的敏感性,并增加成瘾的风险,因为喂食HFD的小鼠对MDPV的急性治疗有更高的效力,并且对药物表现出对FosB诱导的耐受性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Pharmacological Reports
Pharmacological Reports 医学-药学
CiteScore
8.40
自引率
0.00%
发文量
91
审稿时长
6 months
期刊介绍: Pharmacological Reports publishes articles concerning all aspects of pharmacology, dealing with the action of drugs at a cellular and molecular level, and papers on the relationship between molecular structure and biological activity as well as reports on compounds with well-defined chemical structures. Pharmacological Reports is an open forum to disseminate recent developments in: pharmacology, behavioural brain research, evidence-based complementary biochemical pharmacology, medicinal chemistry and biochemistry, drug discovery, neuro-psychopharmacology and biological psychiatry, neuroscience and neuropharmacology, cellular and molecular neuroscience, molecular biology, cell biology, toxicology. Studies of plant extracts are not suitable for Pharmacological Reports.
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