青春期间歇性乙醇暴露与成年大鼠的风险选择增加以及多巴胺能和胆碱能神经元标志物减少有关。
Adolescent intermittent ethanol exposure is associated with increased risky choice and decreased dopaminergic and cholinergic neuron markers in adult rats.
作者信息
Boutros Nathalie, Semenova Svetlana, Liu Wen, Crews Fulton T, Markou Athina
机构信息
Department of Psychiatry, University of California San Diego, La Jolla, California (Drs Boutros, Semenova, Markou); Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (Drs Liu, Crews).
出版信息
Int J Neuropsychopharmacol. 2014 Oct 31;18(2):pyu003. doi: 10.1093/ijnp/pyu003.
BACKGROUND
Binge drinking is prevalent during adolescence and may have effects on the adult brain and behavior. The present study investigated whether adolescent intermittent ethanol exposure alters adult risky choice and prefrontal dopaminergic and forebrain cholinergic neuronal marker levels in male Wistar rats.
METHODS
Adolescent (postnatal day 28-53) rats were administered 5 g/kg of 25% (vol/vol) ethanol 3 times/d in a 2-days-on/2-days-off exposure pattern. In adulthood, risky choice was assessed in the probability discounting task with descending and ascending series of large reward probabilities and after acute ethanol challenge. Immunohistochemical analyses assessed tyrosine hydroxylase, a marker of dopamine and norepinephrine in the prelimbic and infralimbic cortices, and choline acetyltransferase, a marker of cholinergic neurons, in the basal forebrain.
RESULTS
All of the rats preferred the large reward when it was delivered with high probability. When the large reward became unlikely, control rats preferred the smaller, safe reward, whereas adolescent intermittent ethanol-exposed rats continued to prefer the risky alternative. Acute ethanol had no effect on risky choice in either group of rats. Tyrosine hydroxylase (prelimbic cortex only) and choline acetyltransferase immunoreactivity levels were decreased in adolescent intermittent ethanol-exposed rats compared with controls. Risky choice was negatively correlated with choline acetyltransferase, implicating decreased forebrain cholinergic activity in risky choice.
CONCLUSIONS
The decreases in tyrosine hydroxylase and choline acetyltransferase immunoreactivity suggest that adolescent intermittent ethanol exposure has enduring neural effects that may lead to altered adult behaviors, such as increased risky decision making. In humans, increased risky decision making could lead to maladaptive, potentially harmful consequences.
背景
暴饮在青少年时期很普遍，可能会对成年后的大脑和行为产生影响。本研究调查了青春期间歇性乙醇暴露是否会改变成年雄性Wistar大鼠的风险选择以及前额叶多巴胺能和前脑胆碱能神经元标记物水平。
方法
青春期（出生后第28 - 53天）大鼠按照2天暴露/2天休息的模式，每天给予3次5 g/kg的25%（体积/体积）乙醇。成年后，通过具有递减和递增系列大奖励概率的概率折扣任务以及急性乙醇激发后评估风险选择。免疫组织化学分析评估了前边缘皮质和下边缘皮质中多巴胺和去甲肾上腺素的标记物酪氨酸羟化酶，以及基底前脑中胆碱能神经元的标记物胆碱乙酰转移酶。
结果
当大奖励以高概率发放时，所有大鼠都更喜欢大奖励。当大奖励变得不太可能时，对照大鼠更喜欢较小的、安全的奖励，而青春期间歇性乙醇暴露的大鼠继续更喜欢有风险的选择。急性乙醇对两组大鼠的风险选择均无影响。与对照组相比，青春期间歇性乙醇暴露的大鼠酪氨酸羟化酶（仅在前边缘皮质）和胆碱乙酰转移酶免疫反应性水平降低。风险选择与胆碱乙酰转移酶呈负相关，提示前脑胆碱能活性降低与风险选择有关。
结论
酪氨酸羟化酶和胆碱乙酰转移酶免疫反应性的降低表明，青春期间歇性乙醇暴露具有持久的神经影响，可能导致成年行为改变，如增加风险决策。在人类中，增加风险决策可能会导致适应不良、潜在有害的后果。
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