Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile; Department of Biomedical Sciences, University of Padua, Italy.
Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.
Prog Neuropsychopharmacol Biol Psychiatry. 2024 Jul 13;133:111001. doi: 10.1016/j.pnpbp.2024.111001. Epub 2024 Mar 31.
While there is extensive research on alcohol dependence, the factors that make an individual vulnerable to developing alcoholism haven't been explored much. In this study, we aim to investigate how neonatal exposure to sex hormones affects alcohol intake and the regulation of the mesolimbic pathway in adulthood. The study aimed to investigate the impact of neonatal exposure to a single dose of testosterone propionate (TP) or estradiol valerate (EV) on ethanol consumption in adult rats. The rats were subjected to a two-bottle free-choice paradigm, and the content of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens (NAcc) was measured using HPLC-ED. The expression of critical DA-related proteins in the mesolimbic pathway was evaluated through RT-qPCR and western blot analysis. Supraphysiological neonatal exposure to EV or TP resulted in increased ethanol intake over four weeks in adulthood. In addition, the DA and DOPAC content was reduced and increased in the NAcc of EV and TP-treated rats, and β-endorphin content in the hypothalamus decreased in EV-treated rats. The VTA μ receptor and DA type 2 form short receptor (D) expression were significantly reduced in EV and TP male rats. Finally, in an extended 6-week protocol, the increase in ethanol consumption induced by EV was mitigated during the initial two hours post-naloxone injection. Neonatal exposure to sex hormones is a detrimental stimulus for the brain, which can facilitate the development of addictive behaviors, including alcohol use disorder.
尽管有大量关于酒精依赖的研究，但导致个体易患酒精成瘾的因素尚未得到充分探索。在这项研究中，我们旨在研究新生儿暴露于性激素如何影响成年后对酒精的摄入和中脑边缘通路的调节。该研究旨在调查新生大鼠单次暴露于丙酸睾酮（TP）或戊酸雌二醇（EV）对成年大鼠乙醇消耗的影响。大鼠采用双瓶自由选择范式，通过 HPLC-ED 测量伏隔核（NAcc）中多巴胺（DA）和 3,4-二羟基苯乙酸（DOPAC）的含量。通过 RT-qPCR 和 Western blot 分析评估中脑边缘通路中关键 DA 相关蛋白的表达。新生期超生理水平暴露于 EV 或 TP 会导致成年后 4 周内乙醇摄入量增加。此外，EV 和 TP 处理大鼠的 NAcc 中 DA 和 DOPAC 含量降低，DOPAC 含量升高，EV 处理大鼠下丘脑的β-内啡肽含量降低。EV 和 TP 雄性大鼠 VTA μ 受体和 DA 型 2 短受体（D）表达明显降低。最后，在一个延长的 6 周方案中，EV 诱导的乙醇消耗增加在纳洛酮注射后最初 2 小时内得到缓解。新生儿暴露于性激素是对大脑的有害刺激，可促进成瘾行为的发展，包括酒精使用障碍。
