We aimed at the further characterization of rats in which SERT gene silencing was achieved by hippocampal injection of a lentiviral vector, carrying three si-RNA to block SERT mRNA at 66% of normal levels. Improved self-control and reduced restlessness were already demonstrated in these rats. Present further studies consisted of male adult rats, bilaterally inoculated within the hippocampus; control rats received lentivirus particles inactivated with heat. Both groups were maintained in isolation for 5 months, starting from inoculation. Neurochemical changes were studied by proton magnetic resonance spectroscopy (1H-MRS): we found increased hippocampal viability and bioenergetic potential; however, rats showed a behaviorally depressive pattern, also characterized by enhanced affiliation. Based on the extent of such effects, the whole lenti-SERT group was divided into two subgroups, termed intermediate- and extreme- phenotype profiles. While all rats had a widespread modification within dorsal/ventral striatum, amygdala, and hypothalamus, only the former subgroup showed an involvement of Raphé medialis, while, for the latter subgroup, an increase of SERT within hippocampus was unexpectedly caused. Within the less-affected "intermediate" rats, hippocampal 5-HT7 receptors were down-modulated, and also similarly within substantia nigra, septum, and neocortex. This picture demonstrates that additional rather than fewer neurobiological changes accompany a lower phenotypic expression. Overall, tapping hippocampal SERT affected the balance between habits versus strategies of coping by promoting morphogenetic processes indicative of a serotonergic fiber plasticity. Supplementary studies about serotonergic dynamics and neurogenesis within fronto-striatal circuits are needed.

中文翻译：

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慢病毒工具对大鼠海马血清素再摄取的解剖和行为影响。

我们旨在进一步表征通过海马注射慢病毒载体实现 SERT 基因沉默的大鼠，该载体携带三种 si-RNA 以阻断 66% 的正常水平的 SERT mRNA。已经在这些大鼠中证明了自我控制的改善和不安的减少。目前的进一步研究包括雄性成年大鼠，双侧接种在海马体内；对照大鼠接受加热灭活的慢病毒颗粒。从接种开始，两组均保持隔离5个月。通过质子磁共振波谱 (1H-MRS) 研究神经化学变化：我们发现海马活力和生物能量增加；然而，大鼠表现出行为抑郁模式，其特征还在于从属关系增强。根据这种影响的程度，整个 lenti-SERT 组被分为两个亚组，称为中间表型和极端表型。虽然所有大鼠的背侧/腹侧纹状体、杏仁核和下丘脑都有广泛的改变，但只有前一个亚组显示出中缝的受累，而后一个亚组意外地导致了海马内 SERT 的增加。在受影响较小的“中间”大鼠中，海马 5-HT7 受体被下调，并且在黑质、隔膜和新皮质内也类似。该图片表明，伴随较低表型表达的神经生物学变化更多而不是更少。总体而言，通过促进表明血清素纤维可塑性的形态发生过程，利用海马 SERT 影响了习惯与应对策略之间的平衡。