The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens.
The Effects of Maternal Separation on Adult Methamphetamine Self-Administration, Extinction, Reinstatement, and MeCP2 Immunoreactivity in the Nucleus Accumbens.
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DOI：
10.3389/fpsyt.2013.00055
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发表时间：
2013
影响因子：
4.7
通讯作者：
Olive MF
中科院分区：
文献类型：
--
作者：
Lewis CR;Staudinger K;Scheck L;Olive MF
母亲分离（MS）范式是早期生活应激的动物模型。在生命的前2周期间经受MS的动物显示成年后改变的行为和神经内分泌应激反应。MS还产生对包括可卡因、乙醇和安非他明在内的各种滥用药物的反应性改变和自我给药（SA）。然而，还没有研究检查MS对甲基苯丙胺（METH）SA的影响。本研究旨在研究MS对成年期METH SA获得、消退和METH寻求行为恢复的影响。鉴于已知的早期生活压力和药物暴露对表观遗传过程的影响，我们还研究了组间差异的表观遗传标记甲基CpG结合蛋白2（MeCP 2）的水平，在核神经元（NAc）的核心。Long-Evans幼仔和母鼠在出生后第2-14天（PND）分离180分钟（MS 180）或15分钟（MS 15）。从PND 67开始，允许雄性后代获得METH SA（0.05 mg/kg/输注），每天15次，每次2小时，然后进行消退训练和提示诱导的METH寻求行为恢复。然后通过免疫组织化学评估大鼠NAc核心中的MeCP 2水平。MS 180组自我给药的METH显著多于MS 15组，并且获得SA的时间早于MS 15组。未观察到消退或提示诱导的恢复的组间差异。与MS 180大鼠相比，MS 15大鼠NAc核心中MeCP 2免疫反应性细胞显著升高。总之，这些数据表明，MS对METH SA以及大脑奖励回路中的表观遗传过程具有持久的影响。
The maternal separation (MS) paradigm is an animal model of early life stress. Animals subjected to MS during the first 2 weeks of life display altered behavioral and neuroendocrinological stress responses as adults. MS also produces altered responsiveness to and self-administration (SA) of various drugs of abuse including cocaine, ethanol, and amphetamine. However, no studies have yet examined the effects of MS on methamphetamine (METH) SA. This study was performed to examine the effects of MS on the acquisition of METH SA, extinction, and reinstatement of METH-seeking behavior in adulthood. Given the known influence of early life stress and drug exposure on epigenetic processes, we also investigated group differences in levels of the epigenetic marker methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) core. Long–Evans pups and dams were separated on postnatal days (PND) 2–14 for either 180 (MS180) or 15 min (MS15). Male offspring were allowed to acquire METH SA (0.05 mg/kg/infusion) in 15 2-h daily sessions starting at PND67, followed by extinction training and cue-induced reinstatement of METH-seeking behavior. Rats were then assessed for MeCP2 levels in the NAc core by immunohistochemistry. The MS180 group self-administered significantly more METH and acquired SA earlier than the MS15 group. No group differences in extinction or cue-induced reinstatement were observed. MS15 rats had significantly elevated MeCP2-immunoreactive cells in the NAc core as compared to MS180 rats. Together, these data suggest that MS has lasting influences on METH SA as well as epigenetic processes in the brain reward circuitry.