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性荷尔蒙对新生大鼠的程序化作用:对成年雄性和雌性大鼠伏隔核多巴胺 D 受体表达和神经递质释放的影响。

Neonatal programming with sex hormones: Effect on expression of dopamine D receptor and neurotransmitters release in nucleus accumbens in adult male and female rats.

机构信息

Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile; Universidad de Santiago de Chile (USACH), Facultad de Ciencias Médicas, Escuela de Medicina, Centro de Investigación Biomédica y Aplicada (CIBAP), Santiago, Chile.

Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Fisiopatología Integrativa (CENFI), Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso, Chile.

出版信息

Eur J Pharmacol. 2021 Jul 5;902:174118. doi: 10.1016/j.ejphar.2021.174118. Epub 2021 Apr 24.

Abstract

Steroid sex hormones produce physiological effects in reproductive and non-reproductive tissues, such as the brain. In the brain, sex hormones receptors are expressed in cortical, limbic and midbrain areas modulating memory, arousal, fear and motivation between other behaviors. One neurotransmitters system regulated by sex hormones is dopamine (DA), where during adulthood, sex hormones promote neurophysiological and behavioral effects on DA systems such as tuberoinfundibular (prolactin secretion), nigrostriatal (motor circuit regulation) and mesocorticolimbic (driving of motivated behavior). However, the long-term effects induced by neonatal exposure to sex hormones on DA release induced by D receptor activation and its expression in nucleus accumbens (NAcc) have not been fully studied. To answer this question, neurochemical, cellular and molecular techniques were used. The data show sex differences in NAcc DA extracellular levels induced by D receptor activation and protein content of this receptor in male and female control rats. In addition, neonatal programming with a single dose of TP increases the NAcc protein content of D receptors of adult male and female rats. Our results show new evidence related with sex differences that could explain the dependence to drug of abuse in males and females, which may be associated with increased reinforcing effects of drugs of abuse.

摘要

甾体性激素在生殖和非生殖组织(如大脑)中产生生理效应。在大脑中,性激素受体存在于皮质、边缘和中脑区域,调节记忆、觉醒、恐惧和动机等行为。多巴胺(DA)是一种受性激素调节的神经递质系统,在成年期,性激素会对 DA 系统产生神经生理和行为效应,如结节漏斗(催乳素分泌)、黑质纹状体(运动回路调节)和中脑边缘皮质(驱动动机行为)。然而,新生儿暴露于性激素对 D 受体激活诱导的 DA 释放及其在伏隔核(NAcc)中的表达所产生的长期影响尚未得到充分研究。为了回答这个问题,我们使用了神经化学、细胞和分子技术。数据显示,雄性和雌性对照大鼠中,D 受体激活诱导的 NAcc DA 细胞外水平和该受体的蛋白含量存在性别差异。此外,TP 单次剂量编程会增加成年雄性和雌性大鼠 NAcc 中 D 受体的蛋白含量。我们的结果提供了与性别差异相关的新证据,这可能解释了男性和女性对滥用药物的依赖,这可能与滥用药物的强化作用增加有关。

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