Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice

Effects of bingeing on fat during adolescence on the reinforcing effects of cocaine in adult male mice
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DOI:
10.1016/j.neuropharm.2016.09.020
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发表时间:
2017-02-01
期刊:
影响因子:
4.7
通讯作者:
Rodriguez-Arias, Marta
Rodriguez-Arias, Marta
中科院分区:
医学2区
文献类型:
--
作者:
Carmen Blanco-Gandia, M.;Cantacorps, Lidia;Rodriguez-Arias, Marta

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暴饮暴食是暴饮暴食的一种特殊形式,其特征是间歇性过度进食。除了改变神经生物学奖励系统外,一些研究还强调,食用可口的食物会增加对药物使用的脆弱性。本研究旨在探讨青春期高脂饮食对可卡因强化效应的影响,以青春期雄性小鼠为研究对象,每周3天(PND 29-69),连续2 h,连续40 d,观察可卡因对条件性位置偏爱和静脉自我给药范式的强化效应。循环中的瘦素和生长激素释放肽水平以及暴饮暴食对伏隔核(NAcc)和大脑被盖区(VTA)中CB 1 μ阿片受体(莫尔)和生长激素释放肽受体(GHSR)基因表达的影响也进行了评估。高脂狂欢(HFB)的动物更敏感的阈下剂量的可卡因的增强作用的范例分析,和动物下的脂肪戒断更容易恢复条件性位置偏爱。HFB小鼠还表现出可卡因自我给药增强。在脂肪戒断后,暴露于新的脂肪狂欢恢复了可卡因寻求。虽然HFB没有修改瘦素水平,血浆生长激素释放肽的减少。此外,这种模式的脂肪饮食导致减少莫尔和CB 1基因表达的NAcc和增加GHSR的表达在VTA.We建议,在青春期暴饮暴食的脂肪通过大脑奖赏回路,这使个人倾向于寻求可卡因在成年期的敏感化,在大脑中引起持久的变化。(C)2016爱思唯尔有限公司版权所有
Binge eating is a specific form of overeating characterized by intermittent excessive eating. In addition to altering the neurobiological reward system, several studies have highlighted that consumption of palatable food increases vulnerability to drug use. The aim of the present study was to evaluate the effects of a high-fat diet consumed in a binge pattern during adolescence on the reinforcing effects of cocaine.After 40 days of binge-eating for 2 h, three days a week (PND 29-69), the reinforcing effects of cocaine on conditioning place preference and intravenous self-administration paradigm were evaluated in adolescent male mice. Circulating leptin and ghrelin levels and the effects of bingeing on fat on CB1 mu opioid receptor (MOr) and ghrelin receptor (GHSR) gene expression in the Nucleus Accumbens (NAcc) and Ventral Tegmental Area (VTA) were also assessed.Our results showed a significant escalation in the consumption of a high-fat diet between the first and last week. High-fat binge (HFB) animals were more sensitive to the reinforcing effects of a subthreshold dose of cocaine in the paradigms assayed, and animals under fat withdrawal were more vulnerable to the reinstatement of conditioned place preference. HFB mice also showed enhanced cocaine self administration. After fat withdrawal, exposure to a new fat binge reinstated cocaine seeking. Although HFB did not modify leptin levels, a decrease in plasmatic ghrelin was observed. Moreover, this pattern of fatty diet resulted in a reduction of MOr and CB1 gene expression in the NAcc and an increase in GHSR expression in the VTA.We propose that bingeing on fat during adolescence induces long-lasting changes in the brain through the sensitization of brain reward circuits, which predisposes individuals to seek cocaine during adulthood. (C) 2016 Elsevier Ltd. All rights reserved.