Ishihara T, Akiyama K, Kashihara K, Ujike H, Hamamura T, Okada S, Kuroda S
Department of Neuropsychiatry, Okayama University Medical School, Japan.
J Neurochem. 1996 Aug;67(2):708-16. doi: 10.1046/j.1471-4159.1996.67020708.x.
The activator protein-1 (AP-1) binding activities increased in three brain regions (striatum, nucleus accumbens, and cingulate cortex) after a single methamphetamine (METH) injection to rats. Pretreatment with SCH 23390, but not (-)-eticlopride, significantly inhibited the enhanced AP-1 binding activities induced by acute METH administration. The magnitude of enhancement of AP-1 binding activities 3 h after the last dose of chronic METH administration (4 mg/kg once daily for 14 days) was significantly attenuated as compared with those 3 h after a single METH administration. The AP-1 binding activities after a 1-, but not 4-, week abstinence from chronic administration of METH were still significantly higher than those of the saline-treated controls. A METH challenge after a 4-week abstinence period induced significantly lower AP-1 binding activities in rats chronically injected with METH than in rats chronically injected with saline. The supershift assay revealed that the levels of Jun family protein, but not Fos-related antigen, increased significantly in the striatum and nucleus accumbens of chronically METH-treated rats after a 1-week abstinence. These results suggest that chronic METH administration leads to delayed decay of the induced AP-1 binding activities and Jun component levels after abstinence for up to 1 week but results in no change in or decreases these activities and attenuates METH challenge-induced AP-1 binding activities after abstinence for 4 weeks.
给大鼠单次注射甲基苯丙胺（METH）后，三个脑区（纹状体、伏隔核和扣带回皮质）中的活化蛋白-1（AP-1）结合活性增加。用SCH 23390预处理可显著抑制急性给予METH诱导的AP-1结合活性增强，但（-）-埃替氯必利则无此作用。与单次给予METH 3小时后的情况相比，末次给予慢性METH（4mg/kg，每日一次，共14天）后3小时，AP-1结合活性的增强幅度显著减弱。慢性给予METH后，戒断1周而非4周后，AP-1结合活性仍显著高于生理盐水处理的对照组。在4周戒断期后给予METH激发，与慢性注射生理盐水的大鼠相比，慢性注射METH的大鼠诱导的AP-1结合活性显著降低。超迁移分析显示，在慢性给予METH的大鼠戒断1周后，纹状体和伏隔核中Jun家族蛋白水平显著升高，而Fos相关抗原水平无显著变化。这些结果表明，慢性给予METH导致戒断长达1周后诱导的AP-1结合活性和Jun成分水平延迟衰减，但在戒断4周后，这些活性无变化或降低，并减弱了METH激发诱导的AP-1结合活性。
