Psychoneuroimmunology Laboratory, Program in Environmental and Experimental Pathology, Paulista University, São Paulo, Brazil.
CEEpiRG - Center for Epigenetic Study and Genic Regulation, Program in Environmental and Experimental Pathology, Paulista University, São Paulo, Brazil; Experimental and Comparative Pathology, Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, Brazil.
Behav Brain Res. 2023 Aug 24;452:114562. doi: 10.1016/j.bbr.2023.114562. Epub 2023 Jun 30.
The mutant bate-palmas ("claps"; symbol - bapa) mice induced by the mutagenic chemical ENU present motor incoordination and postural alterations. A previous study showed that bapa mice present increased motor/exploratory behaviors during the prepubertal period due to increased striatal tyrosine hydroxylase expression, suggesting striatal dopaminergic system hyperactivity. This study aimed to evaluate the involvement of striatal dopaminergic receptors in the hyperactivity of bapa mice. Male bapa mice and their wild strain (WT) were used. Spontaneous motor behavior was observed in the open-field test, and stereotypy was evaluated after apomorphine administration. The effects of DR1 and DR2 dopaminergic antagonists (SCH-23,390; sulpiride) and the striatal DR1 and D2 receptor gene expression were evaluated. Relative to WT, bapa mice showed: 1) increased general activity for four days; 2) increased rearing and sniffing behavior and decreased immobility after apomorphine; 3) blockage of rearing behavior after the DR2 antagonist but no effect after DR1 antagonist; 4) blockage of sniffing behavior after the DR1 antagonist in bapa and WT mice but no effect after the DR2 antagonist; 5) increased immobility after the DR1 antagonist but no effect after the DR2 antagonist; 6) increased expression of striatal DR1 receptor gene and reduced the DR2 expression gene after apomorphine administration. Bapa mice showed increased activity in open field behavior. The increased rearing behavior induced by apomorphine of bapa mice resulted from the increased gene expression of the DR1 receptor.
ENU 诱变化学物质诱导的突变 bat-palmas（“拍手”；符号-bapa）小鼠表现出运动协调障碍和姿势改变。先前的研究表明，bapa 小鼠在青春期前由于纹状体酪氨酸羟化酶表达增加而表现出增加的运动/探索行为，提示纹状体多巴胺能系统过度活跃。本研究旨在评估纹状体多巴胺受体在 bapa 小鼠过度活跃中的作用。使用雄性 bapa 小鼠及其野生型（WT）。在旷场测试中观察自发运动行为，并在给予阿扑吗啡后评估刻板行为。评估了 DR1 和 DR2 多巴胺能拮抗剂（SCH-23,390；sulpiride）和纹状体 DR1 和 D2 受体基因表达的影响。与 WT 相比，bapa 小鼠表现出：1）持续四天的一般活动增加；2）阿扑吗啡后增加了后肢站立和嗅探行为，减少了不动状态；3）DR2 拮抗剂后阻断了后肢站立行为，但 DR1 拮抗剂无作用；4）DR1 拮抗剂后在 bapa 和 WT 小鼠中阻断了嗅探行为，但 DR2 拮抗剂无作用；5）DR1 拮抗剂后增加了不动状态，但 DR2 拮抗剂无作用；6）阿扑吗啡给药后纹状体 DR1 受体基因表达增加，DR2 表达基因减少。bapa 小鼠在旷场行为中表现出增加的活动。阿扑吗啡诱导的 bapa 小鼠后肢站立行为增加是由于 DR1 受体基因表达增加所致。
