Paternal alcohol exposure reduces acquisition of operant alcohol self-administration and affects Bdnf DNA methylation in male and female offspring.
Paternal alcohol exposure reduces acquisition of operant alcohol self-administration and affects Bdnf DNA methylation in male and female offspring.
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DOI：
10.1111/adb.13078
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Kosten TA
中科院分区：
文献类型：
--
作者：
Nieto SJ;Haile CN;Quave CB;Harding MJ;Nielsen DA;Meisch RA;Kosten TA
酒精使用障碍的家庭传播反映了遗传和环境因素。父亲的酒精暴露可能会影响啮齿动物后代通过表观遗传修饰通过男性生殖系传播。虽然这种暴露会改变小鼠后代的酒精敏感性，但没有研究检查它是否会影响大鼠操作性酒精自我给药的发展。我们暴露雄性Wistar大鼠慢性间歇性乙醇蒸汽室（16小时/天，5天/周）或空气6周。8周后，将大鼠与未饮酒的雌性大鼠交配。评估成年酒精和对照父系F1后代获得酒精自我给药，其中在一次杠杆按压（固定比率1或FR 1）后提供增加的酒精浓度（2.5%、5%和10%，v/v）。在酒精会话之前，训练大鼠在FR 1强化时间表下杠杆按压食物递送。在雄性和后代的精子、中脑核（NAc）和内侧前额叶皮质（mPFC）中测定脑源性神经营养因子（Bdnf）基因的DNA甲基化水平。酒精暴露的公畜NAc中Bdnf DNA甲基化水平较低，mPFC中甲基化水平较高。虽然这种模式并没有在后代中重现，但与对照后代相比，酒精父系的两种性别的后代确实显示出异常的BDNF DNA甲基化模式。酒精父系后代自我管理较少的酒精（5%和10%），没有食物反应的组间差异。结果表明，父亲的酒精暴露在怀孕前防止酒精的初始强化作用，但奖励相关的电路中的BDNF甲基化失调的模式没有模仿的变化中看到的父亲。
Familial transmission of alcohol use disorder reflects genetic and environmental factors. Paternal alcohol exposure may affect rodent offspring via epigenetic modifications transmitted through the male germ line. While such exposure alters alcohol sensitivity in mouse offspring, no studies examined if it impacts the development of operant alcohol self-administration in rats. We exposed male (sires) Wistar rats to chronic intermittent ethanol in vapor chambers (16 h/day; 5 days/week) or to air for 6 weeks. Eight weeks later, rats were mated with alcohol-naive females. Adult alcohol- and control-sired F1 offspring were assessed in acquisition of alcohol self-administration in which increasing alcohol concentrations (2.5%, 5%, & 10%, v/v) were delivered after one lever press (fixed ratio 1 or FR1). Prior to alcohol sessions, rats were trained to lever press for food delivery under an FR1 schedule of reinforcement. DNA methylation levels of the brain derived neurotrophic factor (Bdnf) gene were measured in sperm, nucleus accumbens (NAc), and medial prefrontal cortex (mPFC) in sires and in offspring. Alcohol-exposed sires had lower Bdnf DNA methylation levels in NAc and greater methylation levels in mPFC. Although this pattern was not recapitulated in offspring, alcohol-sired offspring of both sexes did show aberrant Bdnf DNA methylation patterns compared to control-sired offspring. Alcohol-sired offspring self-administered less alcohol (5% & 10%) with no group differences in food responding. Results indicate that paternal alcohol exposure prior to conception protects against alcohol’s initial reinforcing effects but the pattern of dysregulated Bdnf methylation in reward-related circuitry did not mimic changes seen in sires.
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DOI：
10.1523/jneurosci.2243-09.2009
发表时间：
2009-10-28
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jeanblanc J;He DY;Carnicella S;Kharazia V;Janak PH;Ron D
通讯作者：
Ron D
影响因子：
2.9
作者：
BURLEY, N
通讯作者：
BURLEY, N
影响因子：
3.4
作者：
CARROLL, ME;LAC, ST
通讯作者：
LAC, ST
影响因子：
3.7
作者：
Knezovich JG;Ramsay M
通讯作者：
Ramsay M
影响因子：
3.6
作者：
HORGER, BA;SHELTON, K;SCHENK, S
通讯作者：
SCHENK, S