Macht Victoria A, Kelly Sandra J, Gass Justin T
Department of Psychology, University of South Carolina, Columbia, SC 29208, USA.
Department of Psychology, University of South Carolina, Columbia, SC 29208, USA.
Behav Brain Res. 2017 Aug 14;332:259-268. doi: 10.1016/j.bbr.2017.06.003. Epub 2017 Jun 6.
Fetal Alcohol Syndrome (FAS) is associated with high rates of drug addiction in adulthood. One possible basis for increased drug use in this population is altered sensitivity to drug-associated contexts. This experiment utilized a rat model of FASD to examine behavioral and neural changes in the processing of drug cues in adulthood. Alcohol was given by intragastric intubation to pregnant rats throughout gestation and to rat pups during the early postnatal period (ET group). Controls consisted of a non-treated group (NC) and a pair-fed group given the intubation procedure without alcohol (IC). On postnatal day (PD) 90, rats from all treatment groups were given saline, 0.3mg/kg, 3.0mg/kg, or 10.0mg/kg cocaine pairings with a specific context in the conditioned place preference (CPP) paradigm. While control animals of both sexes showed cocaine CPP at the 3.0 and 10.0mg/kg doses, ET females also showed cocaine CPP at 0.3mg/kg. This was accompanied by a decrease in c-Fos/GAD cells in the nucleus accumbens (NAc) shell and GAD-only cells in the NAc shell and PFC at this 0.3mg/kg dose. ET males failed to show cocaine CPP at the 3.0mg/kg dose. This was associated with an increase in c-Fos only-labeled cells in the NAc core and PFC at this 3.0mg/kg dose. These results suggest that developmental alcohol exposure has a sexually-dimorphic effect on cocaine's conditioning effects in adulthood and the NAc.
胎儿酒精综合征(FAS)与成年期药物成瘾的高发生率相关。该人群药物使用增加的一个可能原因是对与药物相关环境的敏感性改变。本实验利用胎儿酒精谱系障碍(FASD)大鼠模型来研究成年期药物线索处理过程中的行为和神经变化。在整个妊娠期通过胃内插管给怀孕大鼠注射酒精,并在出生后早期给幼鼠注射酒精(乙醇暴露组)。对照组包括未处理组(NC)和接受插管操作但未注射酒精的配对喂养组(IC)。在出生后第90天,在条件性位置偏爱(CPP)范式中,给所有处理组的大鼠在特定环境下注射生理盐水、0.3mg/kg、3.0mg/kg或10.0mg/kg可卡因。虽然两性的对照动物在3.0mg/kg和10.0mg/kg剂量下均表现出可卡因CPP,但乙醇暴露组雌性在0.3mg/kg剂量下也表现出可卡因CPP。在0.3mg/kg剂量下,这伴随着伏隔核(NAc)壳中c-Fos/谷氨酸脱羧酶(GAD)细胞以及NAc壳和前额叶皮质(PFC)中仅含GAD细胞的减少。乙醇暴露组雄性在3.0mg/kg剂量下未表现出可卡因CPP。在3.0mg/kg剂量下,这与NAc核心和PFC中仅标记c-Fos的细胞增加有关。这些结果表明,发育过程中的酒精暴露对成年期可卡因的条件作用以及NAc具有性别差异效应。