多巴胺神经元的重复化学遗传激活会导致基线和安非他命诱导的行为发生可逆变化
Muhammad O Chohan1,2, Halli Fein3,4, Sarah Mirro3,4
1Department of Psychiatry, Columbia University Medical Center, New York, NY, 10032, USA. muhammad.chohan@nyspi.columbia.edu.
Psychopharmacology
|August 18, 2023
概括
多巴胺神经元与DREADDs的重复化学遗传激活会导致恒温变化,减少运动和安非他胺反应. 这些神经适应效应在洗后会逆转,突出显示需要在研究中考虑它们.
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.
- 分子生物学分子生物学
背景情况:
- 使用专门由设计药物 (DREADDs) 激活的设计受体进行化学遗传刺激是研究神经回路的常见方法.
- 由于重复使用DREADD激动剂,潜在的恒温适应性尚未得到充分了解.
- 研究这些适应对于解释基于DREADD的研究成果至关重要.
研究的目的:
- 评估多巴胺基 (DA) 神经元的重复DREADD激活对行为和神经元活动的影响.
- 为了确定重复使用DREADD是否会诱导类似于基因操纵的补偿性变化.
- 为了评估这些效应在洗期后的可逆性.
主要方法:
- 在成年TH-Cre小鼠中表达了刺激性hM3D ((Gq) DREADDs.
- 小鼠接受了克洛扎N-氧化物 (CNO) 的重复治疗.
- 评估了运动,刻板印象和DA神经元发射,以及对安非他命 (AMPH) 的反应.
主要成果:
- 在表达DREADD的小鼠中,重复的CNO给药降低了基底运动和AMPH诱导的行为.
- 经过重复的CNO暴露,DA神经元的激发率降低了.
- 一个为期两个月的CNO洗期恢复了正常的运动和AMPH反应.
结论:
- 重复激活DA神经元的DREADD会诱导显著的恒常适应.
- 这些神经适应性变化会影响行为反应和神经元活动.
- 这些发现强调了在电路和行为研究中考虑慢性DREADD效应的重要性.
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