双重DAT和西格玛受体抑制剂减弱了可卡因对核的作用,使大鼠的多巴胺动态减弱
Melinda Hersey1, Maddalena Mereu1, Claire S Jones1
1Medication Development Program, NIDA IRP, Baltimore, MD, USA.
The European journal of neuroscience
|March 6, 2024
概括
多巴胺转运体 (DAT) 和西格玛受体的双抑制剂减少了大鼠大脑中可卡因诱导的多巴胺释放. 这些发现为精神兴奋剂使用障碍 (PSUD) 治疗提供了潜在的治疗点.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 成研究 研究成研究
背景情况:
- 精神兴奋剂使用障碍 (PSUD) 缺乏FDA批准的治疗方法.
- 双重DAT/西格玛受体抑制剂在减少兴奋剂强化方面显示出有前途.
- 可卡因的作用与通过DAT抑制释放多巴胺 (DA) 有关.
研究的目的:
- 为了研究双重DAT/sigma受体抑制剂在可卡因暴露期间对核突 (NAS) 多巴胺动态的神经化学作用.
- 评估特定双重抑制剂 (林卡,SH 3-24,JJC8-091) 对可卡因诱导的DA释放和清除的影响.
主要方法:
- 在体内研究使用微透析和快速扫描循环电压计 (FSCV) 在雄性Sprague Dawley大鼠.
- 在使用可卡因之前,服用林卡,SH 3-24和JJC8-091.
- 测量细胞外多巴胺 (DA) 流量和释放动态在核突 (NAS).
主要成果:
- 林卡和SH 3-24显著降低了可卡因刺激的NAS中的DA流量.
- 林卡和JJC8-091减弱可卡因引起的DA释放,但没有改变DA清除率.
- 双重抑制剂有效调节了与精神刺激作用相关的DA动态.
结论:
- 双DAT/西格玛受体抑制剂通过调节关键神经化学途径,显示出治疗PSUD的潜力.
- 这些化合物改变了可卡因对奖励通路中多巴胺信号传递的影响.
- 对这些抑制剂的进一步研究可能会导致针对兴奋剂成的新型治疗策略.
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