Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation
Increased responsiveness of presumed 5-HT cells to citalopram in adult rats subjected to prolonged maternal separation relative to brief separation
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DOI：
10.1007/s00213-004-1883-x
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发表时间：
2004-11-01
影响因子：
3.4
通讯作者：
Nemeroff, CB
中科院分区：
文献类型：
--
作者：
Arborelius, L;Hawks, BW;Nemeroff, CB
基本原理：童年时期的某些不良事件，如失去父母或性虐待，与日后患抑郁症的可能性增加有关。长期的，每天母亲分离的大鼠幼崽诱导几个行为，内分泌和神经化学的变化类似于人类抑郁症中观察到的。目的：由于脑内多巴胺能系统的功能障碍与抑郁症的病理生理学有关，因此在成年大鼠中研究了新生儿母亲分离对这些系统的影响。方法：从出生后第2天到第14天，雄性大鼠幼仔每天进行180分钟的母体分离（HMS 180）。新生处理大鼠，即，选择在同一时间段（HMS 15）每天分离15分钟的幼鼠作为对照组，因为180分钟的分离涉及幼鼠的处理，即，在分离期间将幼仔从饲养笼中取出。成年大鼠静脉注射西酞普兰（0.05- 0.80mg/kg），观察其对中缝背核（DRN）5-HT神经元放电频率的影响。结果如下：与HMS 15大鼠相比，西酞普兰在0.1 mg/kg和0.4 mg/kg剂量下对HMS 180中的多巴胺能细胞放电的抑制作用显著增强。然而，在DRN的5-HT转运体和5-HT 1A受体的结合位点和mRNA表达的数量并没有在两个饲养组之间的差异。结论：这些结果表明，早期生活压力引起的功能，但不是中央5-HT 1A受体和/或5-HT转运蛋白的密度或mRNA表达的持续变化。
Rationale: Certain adverse events in childhood, such as loss of a parent or sexual abuse, are associated with an increased vulnerability to develop depression later in life. Prolonged, daily maternal separation of rat pups induces several behavioral, endocrine and neurochemical changes similar to those observed in human depression. Objectives: Because dysfunction of brain serotonergic systems has been implicated in the pathophysiology of depression, the effects of neonatal maternal separation on these systems was studied in adult rats. Methods: Male rat pups were subjected to daily maternal separation for 180 min (HMS180) from postnatal day 2 to day 14. Neonatal handled rats, i.e., pups undergoing daily 15-min separations during the same time period (HMS15), were chosen as a control group, since the 180-min separations involved handling of the pups, i.e., the pups were removed from the home cage during the separations. As adults, the effect of citalopram (0.05-0.80 mg/kg, intravenous) on the firing rate of 5-HT neurons in the dorsal raphe nucleus (DRN) was studied. Results: The inhibitory effect of citalopram on serotonergic cell firing was significantly enhanced at doses of 0.1 mg/kg and 0.4 mg/kg in the HMS180 compared with that in the HMS15 rats. However, the number of binding sites and mRNA expression of the 5-HT transporter and 5-HT1A receptors in the DRN did not differ between the two rearing groups. Conclusions: These findings suggest that early life stress gives rise to persistent changes in the function, but not the density or mRNA expression of central 5-HT1A receptors and/or 5-HT transporters.