Maternal fluoxetine impairs synaptic transmission and plasticity in the medial prefrontal cortex and alters the structure and function of dorsal raphe nucleus neurons in offspring mice

IF 3.3 3区心理学 Q1 BEHAVIORAL SCIENCES

Pharmacology Biochemistry and Behavior Pub Date : 2024-08-13 DOI:10.1016/j.pbb.2024.173849

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引用次数: 0

Abstract

Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are commonly prescribed to women during pregnancy and breastfeeding despite posing a risk of adverse cognitive outcomes and affective disorders for the child. The consequences of SSRI-induced excess of 5-HT during development for the brain neuromodulatory 5-HT system remain largely unexplored. In this study, an SSRI - fluoxetine (FLX) - was administered to C57BL/6 J mouse dams during pregnancy and lactation to assess its effects on the offspring. We found that maternal FLX decreased field potentials, impaired long-term potentiation, facilitated long-term depression and tended to increase the density of 5-HTergic fibers in the medial prefrontal cortex (mPFC) of female but not male adolescent offspring. These effects were accompanied by deteriorated performance in the temporal order memory task and reduced sucrose preference with no change in marble burying behavior in FLX-exposed female offspring. We also found that maternal FLX reduced the axodendritic tree complexity of 5-HT dorsal raphe nucleus (DRN) neurons in female but not male offspring, with no changes in the excitability of DRN neurons of either sex. While no effects of maternal FLX on inhibitory postsynaptic currents (sIPSCs) in DRN neurons were found, we observed a significant influence of FLX exposure on kinetics of spontaneous excitatory postsynaptic currents (sEPSCs) in DRN neurons. Finally, we report that no changes in field potentials and synaptic plasticity were evident in the mPFC of the offspring after maternal exposure during pregnancy and lactation to a new antidepressant, vortioxetine. These findings show that in contrast to the mPFC, long-term consequences of maternal FLX exposure on the structure and function of DRN 5-HT neurons are mild and suggest a sex-dependent, distinct sensitivity of cortical and brainstem neurons to FLX exposure in early life. Vortioxetine appears to exert fewer side effects with regards to the mPFC when compared with FLX.

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母体氟西汀会损害后代小鼠内侧前额叶皮层的突触传递和可塑性，并改变背侧剑突核神经元的结构和功能。

尽管选择性血清素（5-HT）再摄取抑制剂（SSRIs）有可能对婴儿造成不良认知结果和情感障碍，但它仍是孕期和哺乳期妇女的常用处方药。在发育过程中，SSRI 诱导的 5-HT 过量对大脑神经调节 5-HT 系统的影响在很大程度上仍未得到探讨。在这项研究中，我们在 C57BL/6 J 小鼠妊娠期和哺乳期给母鼠注射了一种 SSRI--氟西汀（FLX），以评估其对后代的影响。我们发现，母体的 FLX 会降低场电位、损害长期电位、促进长期抑郁，并倾向于增加雌性而非雄性青少年后代内侧前额叶皮层（mPFC）中的 5-HTergic 纤维密度。伴随这些影响的是，FLX暴露的雌性后代在时序记忆任务中的表现变差，蔗糖偏好降低，而大理石掩埋行为没有变化。我们还发现，母体FLX降低了雌性后代5-HT背侧剑突核（DRN）神经元轴突树的复杂性，而没有降低雄性后代的轴突树复杂性，但两种性别的DRN神经元的兴奋性都没有发生变化。虽然母体 FLX 对 DRN 神经元的抑制性突触后电流（sIPSCs）没有影响，但我们观察到 FLX 对 DRN 神经元的自发性兴奋性突触后电流（sEPSCs）的动力学有显著影响。最后，我们报告说，母体在妊娠期和哺乳期接触一种新型抗抑郁药物伏替西汀后，子代的 mPFC 场电位和突触可塑性没有发生明显变化。这些研究结果表明，与 mPFC 不同，母体暴露于 FLX 对 DRN 5-HT 神经元的结构和功能造成的长期影响是温和的，并表明皮质和脑干神经元对生命早期暴露于 FLX 的敏感性与性别有关。与 FLX 相比，伏替西汀对 mPFC 的副作用似乎更小。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacology Biochemistry and Behavior 医学-行为科学

CiteScore

6.40

自引率

2.80%

发文量

122

审稿时长

38 days

期刊介绍： Pharmacology Biochemistry & Behavior publishes original reports in the areas of pharmacology and biochemistry in which the primary emphasis and theoretical context are behavioral. Contributions may involve clinical, preclinical, or basic research. Purely biochemical or toxicology studies will not be published. Papers describing the behavioral effects of novel drugs in models of psychiatric, neurological and cognitive disorders, and central pain must include a positive control unless the paper is on a disease where such a drug is not available yet. Papers focusing on physiological processes (e.g., peripheral pain mechanisms, body temperature regulation, seizure activity) are not accepted as we would like to retain the focus of Pharmacology Biochemistry & Behavior on behavior and its interaction with the biochemistry and neurochemistry of the central nervous system. Papers describing the effects of plant materials are generally not considered, unless the active ingredients are studied, the extraction method is well described, the doses tested are known, and clear and definite experimental evidence on the mechanism of action of the active ingredients is provided.