El Rawas Rana, Thiriet Nathalie, Lardeux Virginie, Jaber Mohamed, Solinas Marcello
Institut de Physiologie et Biologie Cellulaires, University of Poitiers, CNRS, 40 avenue du recteur Pineau, Poitiers 86022, France.
Psychopharmacology (Berl). 2009 Apr;203(3):561-70. doi: 10.1007/s00213-008-1402-6. Epub 2008 Nov 14.
Environmental conditions during adolescence, a critical period of brain maturation, can have important consequences on subsequent vulnerability to drugs of abuse. We have recently found that the behavioral effects of cocaine as well as its ability to increase expression of zif-268 are reduced in mice reared in enriched environments (EE).
The present experiments examined whether environmental enrichment has protective influences on the effects of heroin, a drug of addiction whose mechanism of action differs from that of cocaine.
Mice were housed either in standard environments (SE) or in EE from weaning to adulthood before any drug exposure. EE were constituted by big housing cages and contained constantly a running wheel and a small house and four to five toys that were changed once a week with new toys of different shapes and colors. We assessed the influence of EE on the ability of heroin to (1) induce conditioned place preferences, (2) induce behavioral sensitization, (3) increase dopamine levels in the nucleus accumbens (NAc), and (4) increase expression of the immediate early gene zif-268 in the striatum.
Conditioned place preference but not behavioral sensitization was reduced in EE mice compared to SE mice. Heroin induced similar increases in dopamine levels and in the expression of zif-268 in the NAc of EE and SE mice.
The rewarding effects of heroin are blunted by EE and appear to be, at least in part, independent from activation of the mesolimbic system.
青春期是大脑成熟的关键时期,这一时期的环境条件会对后续滥用药物的易感性产生重要影响。我们最近发现,在丰富环境(EE)中饲养的小鼠,可卡因的行为效应及其增加zif-268表达的能力均有所降低。
本实验研究环境丰富化是否对海洛因的作用具有保护作用,海洛因是一种成瘾性药物,其作用机制与可卡因不同。
在任何药物暴露之前,将小鼠从断奶到成年期分别饲养在标准环境(SE)或EE中。EE由大饲养笼组成,持续配备一个跑步轮、一个小房子以及四到五个玩具,每周更换一次,换成不同形状和颜色的新玩具。我们评估了EE对海洛因以下能力的影响:(1)诱导条件性位置偏爱,(2)诱导行为敏化,(3)增加伏隔核(NAc)中的多巴胺水平,以及(4)增加纹状体中即早基因zif-268的表达。
与SE小鼠相比,EE小鼠的条件性位置偏爱降低,但行为敏化未降低。海洛因在EE小鼠和SE小鼠的NAc中诱导多巴胺水平和zif-268表达出现相似的增加。
EE会减弱海洛因的奖赏效应,且这种效应似乎至少部分独立于中脑边缘系统的激活。