Blanco-Gandía M Carmen, Aracil-Fernández Auxiliadora, Montagud-Romero Sandra, Aguilar Maria A, Manzanares Jorge, Miñarro José, Rodríguez-Arias Marta
Departamento de Psicobiología, Facultad de Psicología, Unidad de Investigación Psicobiología de las Drogodependencias, , Universitat de València, Avda. Blasco Ibáñez, 21, 46010, Valencia, Spain.
Instituto de Neurociencias, Universidad Miguel Hernández-CSIC, Alicante, Spain.
Psychopharmacology (Berl). 2017 Aug;234(15):2337-2352. doi: 10.1007/s00213-017-4630-9. Epub 2017 Apr 29.
Preclinical studies report that free access to a high-fat diet (HFD) alters the response to psychostimulants.
The aim of the present study was to examine how HFD exposure during adolescence modifies cocaine effects. Gene expression of CB1 and mu-opioid receptors (MOr) in the nucleus accumbens (N Acc) and prefrontal cortex (PFC) and ghrelin receptor (GHSR) in the ventral tegmental area (VTA) were assessed.
Mice were allowed continuous access to fat from PND 29, and the locomotor (10 mg/kg) and reinforcing effects of cocaine (1 and 6 mg/kg) on conditioned place preference (CPP) were evaluated on PND 69. Another group of mice was exposed to a standard diet until the day of post-conditioning, on which free access to the HFD began.
HFD induced an increase of MOr gene expression in the N Acc, but decreased CB1 receptor in the N Acc and PFC. After fat withdrawal, the reduction of CB1 receptor in the N Acc was maintained. Gene expression of GHSR in the VTA decreased during the HFD and increased after withdrawal. Following fat discontinuation, mice exhibited increased anxiety, augmented locomotor response to cocaine, and developed CPP for 1 mg/kg cocaine. HFD reduced the number of sessions required to extinguish the preference and decreased sensitivity to drug priming-induced reinstatement.
Our results suggest that consumption of a HFD during adolescence induces neurobiochemical changes that increased sensitivity to cocaine when fat is withdrawn, acting as an alternative reward.
临床前研究报告称，自由摄取高脂饮食（HFD）会改变对精神兴奋剂的反应。
本研究的目的是研究青春期暴露于HFD如何改变可卡因的作用。评估了伏隔核（NAcc）和前额叶皮层（PFC）中CB1和μ-阿片受体（MOr）以及腹侧被盖区（VTA）中胃饥饿素受体（GHSR）的基因表达。
从出生后第29天开始让小鼠持续摄取脂肪，并在出生后第69天评估可卡因（1和6mg/kg）对条件性位置偏爱（CPP）的运动（10mg/kg）和强化作用。另一组小鼠在条件化后直至开始自由摄取HFD之前一直喂食标准饮食。
HFD导致NAcc中MOr基因表达增加，但NAcc和PFC中的CB1受体减少。停止摄取脂肪后，NAcc中CB1受体的减少得以维持。VTA中GHSR的基因表达在摄取HFD期间降低，停止摄取后增加。停止摄取脂肪后，小鼠表现出焦虑增加、对可卡因的运动反应增强，并对1mg/kg可卡因产生CPP。HFD减少了消除偏爱所需的实验次数，并降低了对药物引发的复吸的敏感性。
我们的结果表明，青春期摄取HFD会引起神经生化变化，在停止摄取脂肪时增加对可卡因的敏感性，起到替代奖励的作用。
