Sex-specific effects of developmental alcohol exposure on cocaine-induced place preference in adulthood.
Sex-specific effects of developmental alcohol exposure on cocaine-induced place preference in adulthood.
复制标题
发育期酒精暴露对成年期可卡因引起的地方偏好的性别特异性影响。
DOI：
10.1016/j.bbr.2017.06.003
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发表时间：
2017
影响因子：
2.7
通讯作者：
Gass,JustinT
中科院分区：
文献类型：
--
作者：
Macht,VictoriaA;Kelly,SandraJ;Gass,JustinT
胎儿酒精综合症（FAS）与成年期药物成瘾率高有关。这一人群中药物使用增加的一个可能基础是对药物相关环境的敏感性改变。本实验利用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。乙醇通过胃内插管给予妊娠大鼠在整个妊娠期和大鼠仔鼠在出生后早期（ET组）。对照组包括未给药组（NC）和给予无酒精（IC）插管程序的成对喂养组。在出生后（PD）90天，在条件性位置偏爱（CPP）范式中，对所有给药组的大鼠给予生理盐水、0.3 mg/kg、3.0 mg/kg或10.0 mg/kg可卡因配对。虽然两种性别的对照动物在3.0和10.0 mg/kg剂量下均显示可卡因CPP，但ET雌性动物在0.3 mg/kg剂量下也显示可卡因CPP。在0.3 mg/kg剂量下，这伴随着丘脑核（NAc）壳中c-Fos/GAD 67细胞以及NAc壳和PFC中仅GAD 67细胞的减少。ET雄性动物在3.0 mg/kg剂量下未显示可卡因CPP。这与3.0 mg/kg剂量下NAc核心和PFC中仅c-Fos标记的细胞增加有关。这些结果表明，发育酒精暴露有一个性别的二态性影响可卡因的条件作用在成年期和NAC。
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, 0.3 mg/kg, 3.0 mg/kg, or 10.0 mg/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 10.0 mg/kg doses, ET females also showed cocaine CPP at 0.3 mg/kg. This was accompanied by a decrease in c-Fos/GAD67cells in the nucleus accumbens (NAc) shell and GAD67-only cells in the NAc shell and PFC at this 0.3 mg/kg dose. ET males failed to show cocaine CPP at the 3.0 mg/kg dose. This was associated with an increase in c-Fos only-labeled cells in the NAc core and PFC at this 3.0 mg/kg dose. These results suggest that developmental alcohol exposure has a sexually-dimorphic effect on cocaine’s conditioning effects in adulthood and the NAc.