Adolescent Intermittent Ethanol Increases the Sensitivity to the Reinforcing Properties of Ethanol and the Expression of Select Cholinergic and Dopaminergic Genes within the Posterior Ventral Tegmental Area.

IF 3.2 3区医学 Q1 Medicine Alcoholism, clinical and experimental research Pub Date : 2019-09-01 Epub Date: 2019-08-21 DOI:10.1111/acer.14150

Sheketha R Hauser, Christopher P Knight, William A Truitt, Robert Aaron Waeiss, Ian S Holt, Gustavo B Carvajal, Richard L Bell, Zachary A Rodd

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Abstract

Background: Although not legally allowed to consume alcohol, adolescents account for 11% of all alcohol use in the United States and approximately 90% of adolescent intake is in the form of an alcohol binge. The adolescent intermittent ethanol (AIE) model developed by the NADIA consortium produces binge-like EtOH exposure episodes. The current experiment examined the effects of AIE on the reinforcing properties of EtOH and genetic expression of cholinergic and dopaminergic factors within the posterior ventral tegmental area (pVTA) in Wistar male and female rats and in male alcohol-preferring (P) rats.

Methods: Rats were exposed to the AIE or water during adolescence, and all testing occurred during adulthood. Wistar control and AIE rats were randomly assigned to groups that self-administered 0 to 200 mg% EtOH. Male P rats self-administered 0 to 100 mg%.

Results: The data indicated that exposure to AIE in both Wistar male and female rats (and male P rats) resulted in a significant leftward shift in dose-response curve for EtOH self-administration into the pVTA. TaqMan array indicated that AIE exposure had divergent effects on the expression of nicotinic receptors (increased a7, reduction in a4 and a5). There were also sex-specific effects of AIE on gene expression; male only reduction in D3 receptors.

Conclusion: Binge-like EtOH exposure during adolescence enhances the sensitivity to the reinforcing properties of EtOH during adulthood which could be part of biological sequelae that are the basis for the deleterious effects of adolescent alcohol consumption on the rate of alcoholism during adulthood.

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青少年间歇性服用乙醇会提高对乙醇强化特性的敏感性，并增加后腹侧被盖区内某些胆碱能和多巴胺能基因的表达。

背景：虽然美国法律不允许青少年饮酒，但青少年饮酒量占美国总饮酒量的 11%，约 90% 的青少年摄入酒精的形式是酗酒。由 NADIA 联盟开发的青少年间歇性乙醇（AIE）模型会产生类似狂欢的乙醇暴露事件。本实验研究了AIE对EtOH强化特性的影响，以及Wistar雄性和雌性大鼠和雄性酒精偏好（P）大鼠腹侧被盖后区（pVTA）胆碱能和多巴胺能因子的遗传表达：方法：大鼠在青春期接触 AIE 或水，所有测试均在成年期进行。Wistar 对照组和 AIE 大鼠被随机分配到自我摄入 0 至 200 mg% EtOH 的组中。雄性P大鼠自行摄入0至100毫克浓度的乙醇：数据显示，Wistar雄性和雌性大鼠（以及雄性P型大鼠）暴露于AIE后，自我给药到pVTA的EtOH的剂量-反应曲线显著左移。TaqMan 阵列表明，暴露于 AIE 会对烟碱受体的表达产生不同的影响（a7 增加，a4 和 a5 减少）。AIE对基因表达的影响也有性别特异性；只有男性的D3受体减少：结论：青春期大量接触乙醇会增强成年后对乙醇强化特性的敏感性，这可能是青春期饮酒对成年后酗酒率产生有害影响的部分生物学后遗症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alcoholism, clinical and experimental research 医学-药物滥用

CiteScore

5.90

自引率

9.40%

发文量

219

审稿时长

1 months

期刊介绍： Alcoholism: Clinical and Experimental Research''s scope spans animal and human clinical research, epidemiological, experimental, policy, and historical research relating to any aspect of alcohol abuse, dependence, or alcoholism. This journal uses a multi-disciplinary approach in its scope of alcoholism, its causes, clinical and animal effect, consequences, patterns, treatments and recovery, predictors and prevention.