...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Neuropsychopharmacology >Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration
【24h】

Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration

机译：慢性可卡因自我管理后D1和D2多巴胺受体行为反应的成瘾相关变化

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The cocaine-addicted phenotype can be modeled in rats based on individual differences in preferred levels of cocaine intake and a propensity for relapse in withdrawal. These cocaine-taking and -seeking behaviors are strongly but differentially regulated by postsynaptic D1 and D2 receptors in the mesolimbic dopamine system. Thus, we determined whether addiction-related differences in cocaine self-administration would be related to differential sensitivity in functional D1 and D2 receptor responses. Using a population of 40 outbred Sprague–Dawley rats trained to self-administer cocaine for 3 weeks, we found that animals with higher preferred levels of cocaine intake exhibited a vertical and rightward shift in the self-administration dose–response function, and were more resistant to extinction from cocaine self-administration, similar to phenotypic changes reported in other models of cocaine addiction. After 3 weeks of withdrawal from cocaine self-administration, high intake rats were subsensitive to the ability of the D1 agonist SKF 81297 to inhibit cocaine-seeking behavior elicited by cocaine priming, but supersensitive to cocaine seeking triggered by the D2 agonist quinpirole, when compared to low intake rats. Additionally, high intake rats developed profound increases in locomotor responses to D2 receptor challenge from early to late withdrawal times, whereas low intake rats developed increased responsiveness to D1 receptor challenge. In a second experiment, responses to the mixed D1/D2 agonist apomorphine and the NMDA glutamate receptor antagonist MK-801 failed to differ between low and high intake rats. These findings suggest that cocaine addiction is related specifically to differential alterations in functional D1 and D2 receptors and their ability to modulate cocaine-seeking behavior.
机译：可卡因上瘾的表型可以根据可卡因摄入量的优选水平的个体差异和戒断的复发倾向在大鼠中建模。这些可卡因的摄取和寻求行为受到中脑边缘多巴胺系统中突触后D1和D2受体的强烈但有差异的调节。因此，我们确定了可卡因自我管理中与成瘾相关的差异是否与功能性D1和D2受体反应的敏感性差异有关。通过对40只自交可卡因进行训练的近交Sprague-Dawley大鼠种群进行3周的研究，我们发现，可卡因摄入量偏高的动物在自我给药的剂量-反应功能中表现出垂直和向右移动，并且表现出更多的可卡因。可卡因自我给药对灭绝具有抵抗力，类似于其他可卡因成瘾模型中报告的表型变化。停用可卡因自我给药3周后，高摄入量大鼠对D1激动剂SKF 81297抑制可卡因引发引发的可卡因寻求行为的能力不敏感，但与D2激动剂喹吡罗引发的可卡因寻求超敏感低摄入量的大鼠。此外，高摄入量大鼠从早期到晚期戒断时间对D2受体激发的运动反应均显着增加，而低摄入量大鼠对D1受体激发的反应性增强。在第二个实验中，低摄入量和高摄入量大鼠对混合的D1 / D2激动剂阿扑吗啡和NMDA谷氨酸受体拮抗剂MK-801的反应没有差异。这些发现表明可卡因成瘾与功能性D1和D2受体的差异性变化及其调节可卡因寻求行为的能力有关。

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