Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 26/28 Krakowskie Przedmieście Str., 00-927 Warsaw, Poland.
Behav Brain Res. 2012 Jan 1;226(1):87-95. doi: 10.1016/j.bbr.2011.08.030. Epub 2011 Aug 30.
Recent studies have shown that neurodevelopmental disturbances in the structure and function of the brain are significant factors in the onset of psychiatric disorders. Such deficits may also affect neurotransmission. Among the different neurotransmitter systems, serotonin (5-HT) plays an important role in the organisation and maturation of brain structures during development. The aim of the present study was to examine the influence of neonatal 5-HT depletion on emotional and exploratory behaviours in adult rats. Three-day-old Wistar male rats received intraventricular injections of the selective serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). Littermates given saline injections acted as controls. After three months, rat behaviour was analysed in an open field test, a social interaction test and a novel object test. Moreover, contextual-conditioned freezing and ultravocalisation fear responses were studied. The pain reactivity was measured in a flinch-jump test. Biochemical analysis of 5,7-DHT-treated rats revealed a significant decrease in the concentration of 5-HT and its metabolite in the frontal cortex, hippocampus and striatum, with a decreased dopamine level in striatum. Early serotonin depletion reduced locomotor activity in the open field test and attenuated social interaction in non-aversive conditions and exploration of a novel object in adult rats. Ultravocalisation, but not freezing, was increased in the contextual fear-conditioning paradigm in 5-HT-depleted rats. There was no difference in the pain threshold between groups. These data demonstrate that neonatal 5-HT depletion resulted in subtle alterations in the locomotor, exploratory and conditioned fear response of adult animals.
最近的研究表明，大脑结构和功能的神经发育障碍是精神疾病发病的重要因素。这些缺陷也可能影响神经递质的传递。在不同的神经递质系统中，血清素（5-HT）在大脑结构的发育和成熟过程中起着重要作用。本研究旨在探讨新生期 5-HT 耗竭对成年大鼠情绪和探索行为的影响。3 日龄雄性 Wistar 大鼠接受脑室注射选择性 5-羟色胺神经毒素 5,7-二羟基色胺（5,7-DHT）。接受生理盐水注射的同窝大鼠作为对照。三个月后，在旷场试验、社交互动试验和新物体试验中分析大鼠行为。此外，还研究了情境条件性冻结和超发声恐惧反应。在畏缩跳跃试验中测量疼痛反应性。5,7-DHT 处理大鼠的生化分析显示，前额叶皮层、海马体和纹状体中的 5-HT 及其代谢物浓度显著降低，纹状体中的多巴胺水平降低。早期 5-HT 耗竭减少了旷场试验中的运动活动，减弱了非威胁性条件下的社交互动和成年大鼠对新物体的探索。在 5-HT 耗竭大鼠的情境恐惧条件反射范式中，超发声增加，但冻结减少。两组之间的疼痛阈值没有差异。这些数据表明，新生期 5-HT 耗竭导致成年动物的运动、探索和条件恐惧反应出现细微改变。
