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诺龙会改变青春期前雄性大鼠对可卡因的行为反应以及纹状体和皮质多巴胺受体。

Nandrolone alters the behavioral response to cocaine as well as striatal and cortical dopamine receptors of prepubertal male rats.

作者信息

Freire-Arvelo Jaime A, Rivero Carlos J, Santiago-Marrero Iván G, Mendez-Morales Andrea, González-Segarra Amanda J, Pérez-Cardona Enrique U, Torres-Ramirez Ricardo J, Segarra Annabell C

机构信息

Department of Physiology, School of Medicine, University of Puerto Rico, Medical Sciences Campus, P.O. Box 365067, San Juan, 00936-5067, Puerto Rico.

出版信息

Sci Rep. 2025 Sep 26;15(1):33205. doi: 10.1038/s41598-025-17890-6.

DOI:10.1038/s41598-025-17890-6
PMID:41006530
Abstract

Nandrolone, is an anabolic androgenic steroid (AAS) used by adolescents and young adults. Supraphysiologic doses of AAS are correlated with dysfunctions in anxiety and reward. This study examined whether exposure to nandrolone before puberty altered anxiety- and addictive-like behaviors. Dopamine type 2 receptors (D2DR) in the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) were also analyzed. Beginning on day 28 and ending on day 37, male rats received a daily injection of nandrolone decanoate (20 mg/kg) and were subsequently evaluated for anxiety. Their locomotor response (sensitization) and preference (conditioned place preference (CPP) to cocaine (15 mg/kg) were also assessed. Nandrolone reduced anxiety and ambulation, accelerated the development of sensitization to cocaine, and reduced CPP to cocaine by 27%. Expression of D2DR in the NAc and the PFC of males was increased by nandrolone, whereas treatment with cocaine reduced accumbal D2DR. We hypothesize that nandrolone accelerated the development of the neural circuitry that participates in behavioral sensitization and reduced the rewarding properties of cocaine. The observed increase in accumbal D2DR may have potentially mediated the reduction in anxiety and ambulation and hastened the maturation of the neural circuitry responsible for the sensitized response to cocaine.

摘要

诺龙是一种合成代谢雄激素类固醇(AAS),被青少年和年轻人使用。超生理剂量的AAS与焦虑和奖赏功能障碍相关。本研究考察了青春期前接触诺龙是否会改变焦虑样行为和成瘾样行为。同时还分析了伏隔核(NAc)和内侧前额叶皮质(mPFC)中的多巴胺2型受体(D2DR)。从第28天开始至第37天结束,雄性大鼠每天注射癸酸诺龙(20毫克/千克),随后评估其焦虑情况。还评估了它们的运动反应(敏化)和对可卡因(15毫克/千克)的偏好(条件性位置偏好(CPP))。诺龙减轻了焦虑和活动能力,加速了对可卡因敏化的发展,并使对可卡因的CPP降低了27%。诺龙增加了雄性大鼠NAc和PFC中D2DR的表达,而可卡因治疗则降低了伏隔核中的D2DR。我们推测,诺龙加速了参与行为敏化的神经回路的发育,并降低了可卡因的奖赏特性。观察到的伏隔核D2DR增加可能潜在地介导了焦虑和活动能力的降低,并加速了负责对可卡因敏化反应的神经回路的成熟。

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本文引用的文献

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Anabolic-androgenic steroid use disorder: case for recognition as a substance use disorder with specific diagnostic criteria.合成代谢雄激素类固醇使用障碍:将其认定为具有特定诊断标准的物质使用障碍的理由。
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Dopamine Dysregulation in Reward and Autism Spectrum Disorder.奖励与自闭症谱系障碍中的多巴胺失调
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Social isolation of adolescent male rats increases anxiety and K -induced dopamine release in the nucleus accumbens: Role of CRF-R1.
青春期雄性大鼠的社交隔离会增加伏隔核中的焦虑和 K 诱导的多巴胺释放:CRF-R1 的作用。
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Characteristics and Attitudes of Men Using Anabolic Androgenic Steroids (AAS): A Survey of 2385 Men.男性使用合成代谢雄激素类固醇(AAS)的特征和态度:对 2385 名男性的调查。
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Orexin-A up-regulates dopamine D2 receptor and mRNA in the nucleus accumbens Shell.食欲素 A 上调伏隔核壳部多巴胺 D2 受体和 mRNA。
Mol Biol Rep. 2020 Dec;47(12):9689-9697. doi: 10.1007/s11033-020-05979-2. Epub 2020 Nov 10.
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µ-Opioid receptor-induced synaptic plasticity in dopamine neurons mediates the rewarding properties of anabolic androgenic steroids.µ-阿片受体诱导的多巴胺神经元突触可塑性介导合成代谢雄激素类固醇的奖赏特性。
Sci Signal. 2020 Sep 1;13(647):eaba1169. doi: 10.1126/scisignal.aba1169.
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Genetic Liability for Internalizing Versus Externalizing Behavior Manifests in the Developing and Adult Hippocampus: Insight From a Meta-analysis of Transcriptional Profiling Studies in a Selectively Bred Rat Model.内化与外化行为的遗传易感性在发育和成年海马体中表现出来:来自选择性繁殖大鼠模型转录谱研究的荟萃分析的见解。
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Chronic stress in adolescence differentially affects cocaine vulnerability in adulthood in a selectively bred rat model of individual differences: role of accumbal dopamine signaling.青少年时期的慢性应激在个体差异的选择性繁殖大鼠模型中对成年期可卡因易感性产生不同的影响:伏隔核多巴胺信号的作用。
Stress. 2021 May;24(3):251-260. doi: 10.1080/10253890.2020.1790520. Epub 2020 Aug 4.
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Anabolic androgenic steroid dependence is associated with executive dysfunction.合成代谢雄激素类固醇依赖与执行功能障碍有关。
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