Ahmadi Shamseddin, Amiri Shahin, Rafieenia Fatemeh, Rostamzadeh Jalal
Department of Biological Science and Biotechnology, Faculty of Science, University of Kurdistan, Sanandaj, Iran.
Basic Clin Neurosci. 2013 Spring;4(2):146-52.
Calcium/calmodulin-dependent protein kinase II (CaMKII) which is highly expressed in the hippocampus is known to play a pivotal role in reward-related memories and morphine dependence.
In the present study, repeated morphine injections once daily for 7 days was done to induce morphine tolerance in male Wistar rats, after which gene expression profile of α-isoform of CaMKII (CaMKIIα) in the hippocampus was evaluated upon discontinuation of morphine injection over 21 days of morphine withdrawal. Control groups received saline for 7 consecutive days. For gene expression study, rats' brains were removed and the hippocampus was dissected in separate groups on days 1, 3, 7, 14, and 21 since discontinuation of of morphine injection. A semi-quantitative RT-PCR method was used to evaluate the gene expression profile.
Tolerance to morphine was verified by a significant decrease in morphine analgesia in a hotplate test on day 8 (one day after the final repeated morphine injections). Results showed that gene expression of CaMKIIα at mRNA level on day 1, 3, 7, 14 and 21 of morphine withdrawal was significantly altered as compared to the saline control group. Post hoc Tukey's test revealed a significantly enhanced CaMKIIα gene expression on day 14.
It can be concluded that CaMKIIα gene expression during repeated injections of morphine is increased and this increase continues up to 14 days of withdrawal then settles at a new set point. Therefore, the strong morphine reward-related memory in morphine abstinent animals may, at least partly be attributed to, the up-regulation of CaMKIIα in the hippocampus over 14 days of morphine withdrawal.
钙/钙调蛋白依赖性蛋白激酶II（CaMKII）在海马体中高度表达，已知其在与奖赏相关的记忆和吗啡依赖中起关键作用。
在本研究中，对雄性Wistar大鼠每日注射一次吗啡，连续注射7天以诱导吗啡耐受性，之后在吗啡戒断的21天内，在停止注射吗啡后评估海马体中CaMKIIα异构体的基因表达谱。对照组连续7天接受生理盐水注射。为进行基因表达研究，在停止注射吗啡后的第1、3、7、14和21天，将大鼠处死并取出大脑，将海马体分别分组解剖。采用半定量RT-PCR方法评估基因表达谱。
在第8天（最后一次重复注射吗啡后的一天）的热板试验中，吗啡镇痛作用显著降低，证实了对吗啡的耐受性。结果显示，与生理盐水对照组相比，吗啡戒断第1、3、7、14和21天CaMKIIα的mRNA水平基因表达有显著变化。事后Tukey检验显示，第14天CaMKIIα基因表达显著增强。
可以得出结论，在重复注射吗啡期间CaMKIIα基因表达增加，这种增加持续到戒断14天，然后稳定在一个新的水平。因此，吗啡戒断动物中与强烈吗啡奖赏相关的记忆，至少部分可归因于吗啡戒断14天内海马体中CaMKIIα的上调。
