Compulsive methamphetamine taking and abstinence in the presence of adverse consequences: Epigenetic and transcriptional consequences in the rat brain
Compulsive methamphetamine taking and abstinence in the presence of adverse consequences: Epigenetic and transcriptional consequences in the rat brain
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DOI：
10.1016/j.pbb.2019.02.009
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发表时间：
2019-04-01
影响因子：
3.6
通讯作者：
Jayanthi, Subramaniam
中科院分区：
文献类型：
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作者：
Cadet, Jean Lud;Patel, Ravish;Jayanthi, Subramaniam
甲基苯丙胺成瘾的特点是强迫性的药物摄入狂欢，尽管有不良的生活后果。一种甲基苯丙胺自我给药的模型，包括构成不良后果的应急脚电击，有助于隔离减少或停止甲基苯丙胺的杠杆按压的大鼠（敏感）从那些继续杠杆压力的药物（耐药）我们已经观察到，与对照组相比，耐药大鼠，这表明这些渠道在抑制甲基苯丙胺摄入的作用。戒断一个月后，仅在敏感大鼠的背侧纹状体中，神经生长因子（NGF）表达及其下游信号通路（NGF-TrkA和p75 NTR/MAPK信号通路）也显著增加。与此相反，催产素mRNA的表达增加，只有在神经核的抗性大鼠相比，敏感的大鼠安乐死后的时间。这些结果表明，足电击可以区分两种行为表型的腹侧和背侧纹状体的差异生化和表观遗传的后果。
Methamphetamine addiction is characterized by compulsive binges of drug intake despite adverse life consequences. A model of methamphetamine self-administration that includes contingent footshocks to constitute adverse consequences has helped to segregate rats that reduce or stop lever pressing for methamphetamine (sensitive) from those that continue to lever press for the drug (resistant) in the presence of negative outcomes.We have observed differential DNA hydroxymethylation and increased expression of potassium channel mRNAs in the nucleus accumbens of sensitive compared to resistant rats, suggesting a role of these channels in suppressing methamphetamine intake. There were also significant increases in nerve growth factor (NGF) expression and activation of its downstream signaling pathway (NGF-TrkA and p75NTR/MAPK signaling) in only the dorsal striatum of sensitive rats after a month of abstinence. In contrast, oxytocin mRNA expression was increased in only the nucleus accumbens of resistant rats compared to sensitive rats euthanized after that time. These results indicate that footshocks can differentiate two behavioral phenotypes with differential biochemical and epigenetic consequences in the ventral and dorsal striatum.