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    The aim of this study was to investigate the relationship of dopamine D1 receptor (D1R) and its downstream factors with morphine withdrawal symptoms in rats. Rats were injected intraperitoneally with morphine in a dose-escalating manner. The midbrain periaqueductal gray (PAG) area was microinjected with D1R antagonist SCH23390 or D1R agonist SKF38393. Rats were intraperitoneally injected with naloxone (4 mg/kg) after the last morphine injection, and the withdrawal response was observed. The D1R antagonist reduced the withdrawal response in morphine-exposed rats and decreased the expression of Ca2+/calmodulin-dependent protein kinase II (CaMKII), phosphorylated extracellular signal-regulated kinase (p-ERK) and cAMP response element-binding protein (CREB) in the PAG. However, the ability of SKF38393 to increase the withdrawal response was weak and limited. Taken together, the results suggest that D1R antagonist decreased the withdrawal response in morphine-exposed rats by downregulating the downstream factors, CaMKII, p-ERK and CREB. Copyright © 2019 Elsevier B.V. All rights reserved.


    Qiaofeng Liu, Guizhi Du, Rui Xiao, Yang Liu, Kang Cao, Xiaoyu Du, Shan Tang, Wenli Huang, Xin Wang. Injection of D1 receptor antagonist SCH23390 into the periaqueductal gray attenuates morphine withdrawal symptoms in rats. Neuroscience letters. 2020 Jan 01;714:134502

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    PMID: 31639423

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