Distinct gene alterations between Fos-expressing striatal and thalamic neurons after withdrawal from methamphetamine self-administration
Distinct gene alterations between Fos-expressing striatal and thalamic neurons after withdrawal from methamphetamine self-administration
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DOI：
10.1002/brb3.1378
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发表时间：
2019-07-31
影响因子：
3.1
通讯作者：
Rubio, F. Javier
中科院分区：
文献类型：
--
作者：
Li, Xuan;Davis, Ian R.;Rubio, F. Javier
背景：戒断后对甲基苯丙胺（冰毒）的寻求逐渐增加（冰毒渴求的潜伏期）。我们之前已经证明了丘脑前板间核（AIT）到背内侧纹状体（DMS）投射在这个孵化过程中的作用。在这里，我们检测了在长时间戒断后“孵卵”寻求冰毒复发试验中激活的DMS和AIT神经元的分子变化（由神经元活性标记物Fos识别）。方法对雄性大鼠进行自我注射冰毒或生理盐水（对照组）10天（6小时/天）的训练。使用荧光激活细胞分选，我们检测了fos阳性（在2小时复发试验中激活）和fos阴性（未激活）DMS和AIT神经元的基因表达。结果在DMS中，我们发现与fos阴性神经元相比，fos阳性神经元的即时早期基因（eggs） （Arc、Egr1、Npas4、Fosb）、Trkb、谷氨酸受体亚基（Gria3、Grin1、Grin2b、Grm1）和表观遗传酶（Hdac3、Hdac5、Crebbp）的mRNA表达增加。在AIT中，我们发现少数基因（Egr1、Fosb、TrkB、Grin1和Hdac5）在fos阳性神经元中mRNA表达增加。出乎意料的是，在这两个脑区，上述基因改变也发生在无药生理盐水自我给药的对照大鼠身上。结论这些结果表明，在复发试验中激活的fos阳性神经元的转录调控是脑区域特异性的，但与自我给药训练期间的药物暴露并不唯一相关。
Background Methamphetamine (Meth) seeking progressively increases after withdrawal (incubation of Meth craving). We previously demonstrated a role of anterior intralaminar nucleus of thalamus (AIT) to dorsomedial striatum (DMS) projections in this incubation. Here, we examined molecular alterations in DMS and AIT neurons activated (identified by neuronal activity marker Fos) during "incubated" Meth-seeking relapse test after prolonged withdrawal. Methods We trained male rats to self-administer Meth or saline (control condition) for 10 days (6 hr/day). Using fluorescence-activated cell sorting, we examined gene expression in Fos-positive (activated during a 2-hr relapse test) and Fos-negative (nonactivated) DMS and AIT neurons. Results In DMS, we found increased mRNA expressions of immediate early genes (IEGs) (Arc, Egr1, Npas4, Fosb), Trkb, glutamate receptors subunits (Gria3, Grin1, Grin2b, Grm1), and epigenetic enzymes (Hdac3, Hdac5, Crebbp) in Fos-positive neurons, compared with Fos-negative neurons. In AIT, we found that fewer genes (Egr1, Fosb, TrkB, Grin1, and Hdac5) exhibited increased mRNA expression in Fos-positive neurons. Unexpectedly, in both brain regions, gene alterations described above also occurred in drug-naive saline self-administration control rats. Conclusions These results demonstrated that transcriptional regulations in Fos-positive neurons activated during the relapse tests are brain region-specific but are not uniquely associated with drug exposure during the self-administration training.