Akiyama K, Ishihara T, Kashihara K
Department of Neuropsychiatry, Okayama University Medical School, Japan.
Ann N Y Acad Sci. 1996 Oct 31;801:13-28. doi: 10.1111/j.1749-6632.1996.tb17428.x.
The activator protein-1 (AP-1) binding activities in the three brain regions (striatum, nucleus accumbens, cingulate cortex) increased after a single methamphetamine (METH, 4 mg/kg) injection and reached maximum levels after 180 min. Pretreatment with SCH 23390 (0.5 mg/kg), a selective dopamine D1 receptor antagonist, significantly inhibited the enhanced AP-1 binding activities induced by acute METH (4 mg/kg) administration. In chronic experiments, rats were pretreated with METH (4 mg/kg) or saline for 14 days. The AP-1 binding activities after a 1-week abstinence from chronic administration of MAP increased significantly in all the brain regions compared with those of the saline-treated controls, whereas after a 4-week abstinence, the AP-1 binding activity decreased significantly in the cingulate cortex, but not striatum or nucleus accumbens, compared with the saline-treated control group. A METH challenge after a 4-week abstinence period induced significantly more intense stereotypy, but lower AP-1 binding activities in all the brain regions of rats treated with repeated METH than repeated saline injections. The super-shift assay revealed that after a 1- or 4-week abstinence, there was no significant difference between the Fos-related antigens (Fras) contents of the saline- and METH-treated groups in any brain region examined, and that the Jun family protein levels of the METH-treated group increased significantly in the striatum and nucleus accumbens after a 1-, but not 4-, 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.
单次注射甲基苯丙胺（METH，4毫克/千克）后，三个脑区（纹状体、伏隔核、扣带回皮质）中的活化蛋白-1（AP-1）结合活性增加，并在180分钟后达到最高水平。用选择性多巴胺D1受体拮抗剂SCH 23390（0.5毫克/千克）预处理，可显著抑制急性给予METH（4毫克/千克）诱导的增强的AP-1结合活性。在慢性实验中，大鼠用METH（4毫克/千克）或生理盐水预处理14天。与生理盐水处理的对照组相比，慢性给予MAP后禁欲1周，所有脑区的AP-1结合活性均显著增加；而禁欲4周后，与生理盐水处理的对照组相比，扣带回皮质中的AP-1结合活性显著降低，但纹状体或伏隔核中则没有。禁欲4周后进行METH激发试验，与反复注射生理盐水的大鼠相比，反复给予METH的大鼠在所有脑区中诱导出的刻板行为更强烈，但AP-1结合活性更低。超迁移试验显示，禁欲1周或4周后，在任何检测的脑区中，生理盐水处理组和METH处理组的Fos相关抗原（Fras）含量均无显著差异，且禁欲1周后，METH处理组纹状体和伏隔核中的Jun家族蛋白水平显著升高，但禁欲4周后则没有。这些结果表明，慢性给予METH会导致禁欲长达1周后诱导的AP-1结合活性和Jun成分水平延迟衰减，但禁欲4周后这些活性无变化或降低，并减弱METH激发诱导的AP-1结合活性。
