Iwasa H, Kikuchi S, Hasegawa S, Suzuki K, Sato T
Department of Neuropsychiatry, Chiba University School of Medicine, Japan.
Ann N Y Acad Sci. 1996 Oct 31;801:110-5. doi: 10.1111/j.1749-6632.1996.tb17435.x.
Guanine nucleotide-binding regulatory proteins (G proteins) play an obligatory role in the transmembrane signaling system and are concerned with the neurochemical basis of several psychiatric disorders. We examined the alteration in the mRNA levels of G protein subclasses (Gil alpha, Gi2 alpha and Go alpha) in behavioral sensitized rats using subchronic treatment with methamphetamine (MAP). Adult male Sprague-Dawley rats received intraperitoneal injections of MAP (4 mg/kg) or saline (control) once daily for 14 days. A remarkable increase in the levels of Gi2 alpha mRNA was observed in both sides of striatum at 48 hours after the last injection of MAP. The changes in the Gi2 alpha mRNA levels were not significant at two weeks after the last injection of MAP. The levels of Go alpha and Gil alpha mRNA were not changed at 48 hours and at two weeks after the last injection of MAP. These results suggest that the changes in the Gi2 mRNA level might be responsible for the reinforcement of the generation of stereotyped abnormal behavior by repeated administration of MAP rather than the persistence of the reverse tolerance phenomenon.
鸟嘌呤核苷酸结合调节蛋白（G蛋白）在跨膜信号系统中起关键作用，并与多种精神疾病的神经化学基础有关。我们使用甲基苯丙胺（MAP）亚慢性治疗，研究行为敏化大鼠中G蛋白亚类（Gilα、Gi2α和Goα）mRNA水平的变化。成年雄性Sprague-Dawley大鼠每天腹腔注射一次MAP（4mg/kg）或生理盐水（对照），持续14天。在最后一次注射MAP后48小时，纹状体两侧Gi2αmRNA水平显著升高。在最后一次注射MAP两周后，Gi2αmRNA水平的变化不显著。在最后一次注射MAP后48小时和两周时，Goα和GilαmRNA水平没有变化。这些结果表明，Gi2 mRNA水平的变化可能是反复给予MAP强化刻板异常行为产生的原因，而不是反向耐受现象的持续存在。
