低剂量阿片类药物对大脑区域特定的神经激活促进社会行为
Soichiro Ohnami1,2, Megumi Naito3, Haruki Kawase3
1Laboratory for Drug Discovery and Disease Research, Shionogi & Co. Ltd., Toyonaka, Osaka, Japan.
JCI insight
|December 6, 2024
概括
低剂量的阿片类药物,如吗啡,可以通过激活特定的大脑区域来增强社交行为. 这种方法在治疗自闭症谱系障碍 (ASD) 中的社会缺陷方面具有前景,通过避免激活抑制社会互动的大脑区域.
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.
- 行为科学 行为科学
背景情况:
- 阿片类药物系统显著影响社会行为,但阿片类药物对社会缺陷的确切机制和治疗应用仍然不完全理解.
- 了解不同阿片类药物剂量和受体相互作用如何影响神经回路对于开发向疗法至关重要.
研究的目的:
- 研究片受体激动剂对小鼠社会行为的影响,包括自闭症谱系障碍 (ASD) 类模型.
- 阐明阿片类药物调节的社会行为的基础的神经机制,专注于特定大脑区域的激活.
- 评估选择性阿片类药物激动剂对社会行为缺陷的治疗潜力.
主要方法:
- 在幼稚小鼠和类似自闭症的小鼠模型中利用药理学,行为学和免疫组织学c-Fos绘制技术 (产前治疗酸和Fmr1-KO小鼠).
- 服用低剂量和高剂量吗啡,以评估对社会行为和神经激活模式的剂量依赖影响.
- 通过直接注射dmPAG内部的吗啡来研究背中介外水道灰色 (dmPAG) 的作用.
主要成果:
- 低剂量吗啡通过激活亲社会大脑区域 (例如,核) 而不是dmPAG来促进社会行为.
- 高剂量吗啡激活dmPAG,该区域通过直接注射的激活抵消了低剂量吗啡的亲社会效应,表明其在抑制社会行为的作用.
- 布普伦诺芬是一种局部片激动剂,通过选择性地激活亲社会区域而无需使用dmPAG来改善自闭症类型模型中的社会缺陷.
结论:
- 通过低剂量的阿片类药物选择性激活亲社会大脑区域可以增强社会行为.
- 似乎dmPAG在社会行为中起着抑制作用,因亲社会效应而应避免通过阿片类药物激活dmPAG.
- 针对特定神经回路的阿片类药物策略,就像布普伦诺芬所使用的那样,为ASD的社会行为缺陷提供了一个有希望的治疗途径.
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