Kiiskinen Tuomo, Korpi Esa R, Aitta-Aho Teemu
Department of Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Behav Pharmacol. 2019 Aug;30(5):405-411. doi: 10.1097/FBP.0000000000000449.
Extinction and reinstatement of morphine-induced conditioned place preference were studied in glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-receptor GluA1 subunit-deficient mice (global GluA1-KO mice). In line with previous findings, both acquisition and expression of conditioned place preference to morphine (20 mg/kg, subcutaneously) were fully functional in GluA1 KO mice compared with wild-type littermate controls (GluA1-WT), thus enabling the study of extinction. With a 10-session extinction paradigm, the GluA1 KO mice showed complete extinction similar to that of the GluA1-WT mice. Morphine-induced reinstatement (10 mg/kg, subcutaneously) was detected in both mouse lines. GluA1 KO mice moved more during all the phases of the experiment, including the place conditioning trials, extinction sessions, and place preference tests. The results suggest that the GluA1 subunit may be dispensable or prone to compensation at the neural circuitries delineating extinction and reinstatement. The GluA1 KO mice show altered long-term between-session habituation, which extends longer than previously anticipated.
在谷氨酸α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体GluA1亚基缺陷小鼠（全局GluA1基因敲除小鼠）中研究了吗啡诱导的条件性位置偏好的消退和恢复。与先前的研究结果一致，与野生型同窝对照小鼠（GluA1-WT）相比，GluA1基因敲除小鼠对吗啡（20mg/kg，皮下注射）的条件性位置偏好的获得和表达均功能正常，从而能够进行消退研究。采用10节次的消退范式，GluA1基因敲除小鼠表现出与GluA1-WT小鼠相似的完全消退。在两个小鼠品系中均检测到吗啡诱导的恢复（10mg/kg，皮下注射）。GluA1基因敲除小鼠在实验的所有阶段，包括位置条件试验、消退节次和位置偏好测试中活动更多。结果表明，在描绘消退和恢复的神经回路中，GluA1亚基可能是可有可无的或易于发生代偿。GluA1基因敲除小鼠表现出改变的长期节次间习惯化，其持续时间比先前预期的更长。
