Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats.
Potentiation of glutamatergic synaptic transmission onto lateral habenula neurons following early life stress and intravenous morphine self-administration in rats.
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DOI：
10.1111/adb.13064
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发表时间：
2022-01
影响因子：
3.4
通讯作者：
Nugent FS
中科院分区：
文献类型：
--
作者：
Langlois LD;Berman RY;Shepard RD;Simmons SC;Tsuda MC;Gouty S;Choi KH;Nugent FS
早期生活压力通过对中脑边缘多巴胺通路的持续影响，成为吸毒成瘾以及共病抑郁和焦虑的重要危险因素。我们实验室最近发表的研究成果使用大鼠儿童忽视（单次 24 小时母体剥夺，MD）的早期生活压力模型，表明 MD 会导致腹侧被盖区及其负控制器外侧缰核 (LHb) 功能障碍。 MD诱导的谷氨酸突触传递到LHb神经元的增强将兴奋/抑制（E/I）平衡的协调转向兴奋，导致整体自发神经元活动增加，爆发和强直性放电增加，以及早期青春期雄性大鼠LHb神经元的内在兴奋性。在这里，我们探讨了 MD 如何影响成年雄性大鼠静脉吗啡自我给药 (MSA) 获取和蔗糖偏好以及 LHb 神经元的谷氨酸突触功能。我们发现 MD 诱导的 LHb 神经元和谷氨酸突触活性以及 E/I 比值的增加持续到成年期。此外，MD 显着减少吗啡摄入量，在蔗糖偏好测试中引发快感缺乏样行为，并与最后一次 MSA 疗程后 24 小时持续谷氨酸能增强相关。 MSA 还改变了对照组大鼠 LHb 神经元 AMPAR 电流的衰减时间动力学。我们的数据强调，早期生活压力引起的 LHb 谷氨酸可塑性可能会抑制自然奖励和阿片类药物的积极强化和激励特性，并可能导致与阿片类药物相关的快感缺乏和烦躁状态的发展。
Early life stress presents an important risk factor for drug addiction and comorbid depression and anxiety through persistent effects on the mesolimbic dopamine pathways. Using an early life stress model for child neglect (a single 24 h episode of maternal deprivation, MD) in rats, recent published works from our lab show that MD induces dysfunction in the ventral tegmental area and its negative controller, the lateral habenula (LHb). MD-induced potentiation of glutamatergic synaptic transmission onto LHb neurons shifts the coordination of excitation/inhibition (E/I) balance towards excitation, resulting in an increase in the overall spontaneous neuronal activity with elevation in bursting and tonic firing, and in the intrinsic excitability of LHb neurons in early adolescent male rats. Here, we explored how MD affects intravenous morphine self-administration (MSA) acquisition and sucrose preference as well as glutamatergic synaptic function in LHb neurons of adult male rats self-administering morphine. We found that MD-induced increases in LHb neuronal and glutamatergic synaptic activity and E/I ratio persisted into adulthood. Moreover, MD significantly reduced morphine intake, triggered anhedonia-like behavior in the sucrose preference test, and was associated with persistent glutamatergic potentiation 24h after the last MSA session. MSA also altered the decay time kinetics of AMPAR currents in LHb neurons of control rats during this time period. Our data highlights that early life stress-induced glutamatergic plasticity in LHb may dampen the positive reinforcing and motivational properties of both natural rewards and opioids, and may contribute to the development of anhedonia and dysphoric states associated with opioids.
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影响因子：
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