Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice
Anabolic-androgenic steroid treatment induces behavioral disinhibition and downregulation of serotonin receptor messenger RNA in the prefrontal cortex and amygdala of male mice
复制标题
DOI：
10.1111/j.1601-183x.2008.00458.x
复制
发表时间：
2009-03-01
影响因子：
2.5
通讯作者：
Chiavegatto, S.
中科院分区：
文献类型：
--
作者：
Ambar, G.;Chiavegatto, S.
Nandrolone是一种合成代谢雄激素类固醇（AAS），被寻求增强体力或身体外观的个人高度滥用。这种合成睾酮衍生物的超生理剂量与许多身体和精神方面的不良反应有关，特别是冲动和明显的攻击行为。由于AAS诱导的行为去抑制的神经机制尚不清楚，我们研究了接受长时间诺龙给药的小鼠几个脑区中与多巴胺能系统相关的转录本的状态。雄性C57 BL/6 J小鼠接受15 mg/kg癸酸诺龙皮下注射，每日一次，持续28天，并使用不同的动物组，通过实时定量聚合酶链反应研究运动相关和情绪相关行为或5-HT相关信使RNA（mRNA）水平。注射AAS的小鼠体重增加，更活跃，在新的环境中表现出焦虑样行为。他们在强迫游泳测试中表现出较低的不动性，更有可能具有攻击性，更容易攻击对手。AAS治疗显著降低了杏仁核和前额皮质中大多数研究的突触后5-HT受体的mRNA水平。有趣的是，5-HT 1B mRNA水平在海马和下丘脑中进一步降低。中脑5-HT系统转录水平无明显变化。总之，高剂量的AAS诺龙在雄性小鼠中重现了在滥用者中观察到的行为去抑制。此外，这些高剂量下调杏仁核和前额皮质中的5-HT受体mRNA水平。我们的综合研究结果表明，这些领域的AAS诱导的影响和5-HT 1B受体在所观察到的行为去抑制的可能作用的关键网站。
Nandrolone is an anabolic-androgenic steroid (AAS) that is highly abused by individuals seeking enhanced physical strength or body appearance. Supraphysiological doses of this synthetic testosterone derivative have been associated with many physical and psychiatric adverse effects, particularly episodes of impulsiveness and overt aggressive behavior. As the neural mechanisms underlying AAS-induced behavioral disinhibition are unknown, we investigated the status of serotonergic system-related transcripts in several brain areas of mice receiving prolonged nandrolone administration. Male C57BL/6J mice received 15 mg/kg of nandrolone decanoate subcutaneously once daily for 28 days, and different sets of animals were used to investigate motor-related and emotion-related behaviors or 5-HT-related messenger RNA (mRNA) levels by real-time quantitative polymerase chain reaction. AAS-injected mice had increased body weight, were more active and displayed anxious-like behaviors in novel environments. They exhibited reduced immobility in the forced swim test, a higher probability of being aggressive and more readily attacked opponents. AAS treatment substantially reduced mRNA levels of most investigated postsynaptic 5-HT receptors in the amygdala and prefrontal cortex. Interestingly, the 5-HT1B mRNA level was further reduced in the hippocampus and hypothalamus. There was no alteration of 5-HT system transcript levels in the midbrain. In conclusion, high doses of AAS nandrolone in male mice recapitulate the behavioral disinhibition observed in abusers. Furthermore, these high doses downregulate 5-HT receptor mRNA levels in the amygdala and prefrontal cortex. Our combined findings suggest these areas as critical sites for AAS-induced effects and a possible role for the 5-HT1B receptor in the observed behavioral disinhibition.