Methamphetamine Self-Administration Elicits Sex-Related Changes in Postsynaptic Glutamate Transmission in the Prefrontal Cortex
Methamphetamine Self-Administration Elicits Sex-Related Changes in Postsynaptic Glutamate Transmission in the Prefrontal Cortex
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DOI：
10.1523/eneuro.0401-18.2018
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发表时间：
2019-01-01
期刊：
影响因子：
3.4
通讯作者：
Lavin, Antonieta
中科院分区：
文献类型：
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作者：
Pena-Bravo, Jose Ignacio;Penrod, Rachel;Lavin, Antonieta
临床前和临床研究表明，女性更容易受到兴奋剂的奖励作用，并提出雌激素可能在这种增强的敏感性中发挥作用;然而，甲基苯丙胺（METH）诱导的神经可塑性的性别差异尚未探讨。为了解决这个知识的差距，我们记录了从前额叶皮层（PL-PFC）的雄性和雌性大鼠长时间访问METH自我管理（SA）后，并研究了由此产生的长期突触神经适应。雄性和雌性在SA期间服用相似量的METH;然而，与雄性相比，雌性大鼠表现出显著的突触基线差异。此外，女性表现出显着增加诱发兴奋电流。诱发谷氨酸的增加与NMDA电流的增加相关，并且不受应用GluN 2B选择性阻断剂的影响。我们建议METH SA选择性上调雌性大鼠PFC中缺乏GluN 2B的NMDA受体（NMDAR）。我们的研究结果可能提供了一个机械的解释性别差异报告甲基成瘾的女性。
Preclinical and clinical research has shown that females are more vulnerable to the rewarding effects of stimulants, and it has been proposed that estrogens may play a role in this enhanced sensitivity; however sex differences in methamphetamine (METH)-induced neuroplasticity have not been explored. To address this gap in knowledge, we recorded from the prelimbic area of the prefrontal cortex (PL-PFC) of male and female rats following long access METH self-administration (SA) and investigated the resulting long-term synaptic neuroadaptations. Males and females took similar amounts of METH during SA; however, female rats exhibit significant synaptic baseline differences when compared to males. Furthermore, females exhibited a significant increase in evoked excitatory currents. This increase in evoked glutamate was correlated with increases in NMDA currents and was not affected by application of a GluN2B selective blocker. We propose that METH SA selectively upregulates GluN2B-lacking NMDA receptors (NMDAR) in the PFC of female rats. Our results may provide a mechanistic explanation for the sex differences reported for METH addiction in females.