Canese Rossella, Zoratto Francesca, Altabella Luisa, Porcari Paola, Mercurio Laura, de Pasquale Francesco, Butti Erica, Martino Gianvito, Lacivita Enza, Leopoldo Marcello, Laviola Giovanni, Adriani Walter
Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, viale Regina Elena 299, Rome, 00161, Italy,
Psychopharmacology (Berl). 2015 Jan;232(1):75-89. doi: 10.1007/s00213-014-3639-6. Epub 2014 Jun 13.
The serotonin 7 receptor (5-HT7-R) is part of a neuro-transmission system with a proposed role in neural plasticity and in mood, cognitive or sleep regulation.
We investigated long-term consequences of sub-chronic treatment, during adolescence (43-45 to 47-49 days old) in rats, with a novel 5-HT7-R agonist (LP-211, 0 or 0.250 mg/kg/day).
We evaluated behavioural changes as well as forebrain structural/functional modifications by in vivo magnetic resonance (MR) in a 4.7 T system, followed by ex vivo histology.
Adult rats pre-treated during adolescence showed reduced anxiety-related behaviour, in terms of reduced avoidance in the light/dark test and a less fragmented pattern of exploration in the novel object recognition test. Diffusion tensor imaging (DTI) revealed decreased mean diffusivity (MD) in the amygdala, increased fractional anisotropy (FA) in the hippocampus (Hip) and reduced axial (D||) together with increased radial (D⊥) diffusivity in the nucleus accumbens (NAcc). An increased neural dendritic arborization was confirmed in the NAcc by ex vivo histology. Seed-based functional MR imaging (fMRI) identified increased strength of connectivity within and between "limbic" and "cortical" loops, with affected cross-correlations between amygdala, NAcc and Hip. The latter displayed enhanced connections through the dorsal striatum (dStr) to dorso-lateral prefrontal cortex (dl-PFC) and cerebellum. Functional connection also increased between amygdala and limbic elements such as NAcc, orbito-frontal cortex (OFC) and hypothalamus. MR spectroscopy (1H-MRS) indicated that adolescent LP-211 exposure increased glutamate and total creatine in the adult Hip.
Persistent MR-detectable modifications indicate a rearrangement within forebrain networks, accounting for long-lasting behavioural changes as a function of developmental 5-HT7-R stimulation.
血清素7受体（5-HT7-R）是神经传递系统的一部分，在神经可塑性以及情绪、认知或睡眠调节中发挥作用。
我们研究了在青春期（43 - 45至47 - 49日龄）大鼠中，使用新型5-HT7-R激动剂（LP - 211，0或0.250毫克/千克/天）进行亚慢性治疗的长期后果。
我们通过4.7 T系统中的体内磁共振（MR）评估行为变化以及前脑结构/功能改变，随后进行离体组织学检查。
青春期接受预处理的成年大鼠表现出焦虑相关行为减少，在明暗试验中回避行为减少，在新物体识别试验中探索模式碎片化程度降低。扩散张量成像（DTI）显示杏仁核平均扩散率（MD）降低，海马体（Hip）分数各向异性（FA）增加，伏隔核（NAcc）轴向扩散率（D||）降低以及径向扩散率（D⊥）增加。离体组织学证实NAcc中神经树突分支增加。基于种子点的功能磁共振成像（fMRI）显示“边缘”和“皮质”环路内及之间的连接强度增加，杏仁核、NAcc和Hip之间的交叉相关性受到影响。后者通过背侧纹状体（dStr）与背外侧前额叶皮质（dl-PFC）和小脑之间的连接增强也得以显示。杏仁核与边缘结构如NAcc、眶额叶皮质（OFC）和下丘脑之间的功能连接也增加。磁共振波谱（1H-MRS）表明青春期暴露于LP - 211会使成年Hip中的谷氨酸和总肌酸增加。
持续可通过MR检测到的改变表明前脑网络内发生了重新排列，这解释了作为发育性5-HT7-R刺激函数的持久行为变化。
