...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Behavioral sensitization to amphetamine results from an uncoupling between noradrenergic and serotonergic neurons
【24h】

Behavioral sensitization to amphetamine results from an uncoupling between noradrenergic and serotonergic neurons

机译：对苯丙胺的行为敏化是由于去甲肾上腺素能神经元和血清素能神经元之间的解偶联

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

In rodents, drugs of abuse induce locomotor hyperactivity, and repeating injections enhances this response. This effect, called behavioral sensitization, persists many months after the last administration, thus mimicking long-term sensitivity to drugs observed in human addicts. We show here that, in naive animals, noradrenergic and serotonergic systems, besides their behavioral activating effects, inhibit each other by means of the stimulation of alpha 1b-adrenergic and 5-HT2A receptors and that this mutual inhibition vanishes with repeated injections of d-amphetamine; this uncoupling may be responsible for behavioral sensitization and for an increased reactivity of dopaminergic neurons. First, after repeated d-amphetamine injections, a d-amphetamine challenge induces a dramatic increase in cortical extracellular norepinephrine (NE) levels. This increased cortical NE release still occurs after 1 month of withdrawal but is diminished or blocked if sensitization is performed in the presence of prazosin, SR46349B, or both alpha 1-adrenergic and 5-HT2A receptor antagonists, respectively. A strong correlation between increases in cortical extracellular NE levels and the expression of behavioral sensitization was found. Second, repeated d-amphetamine injections induce an increased reactivity of serotonergic neurons measured by cortical extracellular serotonin (5-HT) levels after the administration of a 5-HT releaser, p-chloroamphetamine. Third, knockout mice for alpha 1b-adrenergic (alpha 1b-AR KO) or 5-HT2A (5-HT2A-R KO) receptor, respectively, exhibit a behavioral and biochemical hyperreactivity to the acute injection of p-chloroamphetamine (alpha 1b-AR KO; 5-HT levels) and d-amphetamine (5-HT2A-R KO; NE levels). Uncoupling between noradrenergic and serotonergic neurons may occur not only in addiction but also during chronic stressful situations, thus facilitating the onset of mental illness.
机译：在啮齿动物中，滥用药物会引起运动亢进，重复注射会增强这种反应。这种效应被称为行为敏化，在最后一次给药后会持续数月，从而模仿了对人类成瘾者中观察到的药物的长期敏感性。我们在这里表明，在幼稚的动物中，去甲肾上腺素能和5-羟色胺能系统除了具有行为激活作用外，还通过刺激α1b-肾上腺素能和5-HT2A受体相互抑制，并且这种相互抑制作用随着重复注射d-而消失。苯丙胺这种解耦可能是行为敏化和多巴胺能神经元反应性增加的原因。首先，在反复注射d-苯丙胺后，d-苯丙胺攻击会引起皮质细胞外去甲肾上腺素（NE）水平急剧增加。停药1个月后，皮质NE释放的增加仍会发生，但是如果分别在prazosin，SR46349B或同时存在α1-肾上腺素和5-HT2A受体拮抗剂的情况下进行敏化，则皮质NE的释放会减少或受阻。发现皮质细胞外NE水平的增加与行为敏化的表达之间有很强的相关性。其次，在注射5-HT释放剂对氯苯丙胺后，重复注射d-苯丙胺会引起血清神经素神经元反应性的提高，该反应是通过皮质细胞外血清素（5-HT）的水平来衡量的。第三，分别针对α1b-肾上腺素（α1b-AR KO）或5-HT2A（5-HT2A-R KO）受体的基因敲除小鼠表现出对急性注射对氯苯丙胺（α1b- AR KO； 5-HT水平）和d-苯异丙胺（5-HT2A-R KO； NE水平）。去甲肾上腺素能神经元和血清素能神经元之间的解偶联不仅可能在成瘾中发生，而且在慢性应激情况下也可能发生，从而促进精神疾病的发作。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号