Department of Environmental Medicine and Epidemiology, Medical University of Silesia, 41-808, Zabrze, Poland.
Neurotox Res. 2011 Aug;20(2):103-8. doi: 10.1007/s12640-010-9217-8. Epub 2010 Sep 14.
The aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats lesioned as neonates with the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At 3 days after birth Wistar rats were pretreated with desipramine (20 mg/kg ip) before bilateral icv administration of 5,7-DHT (37.5 μg base on each side) or saline-ascorbic (0.1%) vehicle (control). At 10 week levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were determined in frontal cortex, striatum, and hippocampus by an HPLC/ED technique. In the hypothalamus, frontal cortex, hippocampus and medulla oblongata, the level of histamine was analyzed by an immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped activity) were performed, and effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists S(+)chlorpheniramine (H(1)), cimetidine (H(2)), and thioperamide (H(3)) were determined. We confirmed that 5,7-DHT profoundly reduced contents of 5-HT and 5-HIAA in the brain in adulthood. Histamine content was also reduced in all examined brain regions. Moreover, in 5,7-DHT-lesioned rats the locomotor and oral activity responses to thioperamide were altered, and apomorphine-induced stereotype was intensified. From the above, we conclude that an intact central serotoninergic system modulates histamine H(3) receptor antagonist effects on the dopaminergic neurons in rats.
这项研究的目的是确定新生期大鼠大脑中的组胺含量以及组胺受体拮抗剂对 5,7-二羟色胺（5,7-DHT）神经毒素损伤成年大鼠行为的影响。在出生后 3 天，Wistar 大鼠先用去甲丙咪嗪（20mg/kg ip）预处理，然后双侧脑室注射 5,7-DHT（每侧 37.5μg 碱基）或生理盐水-抗坏血酸（0.1%）载体（对照）。在 10 周时，通过 HPLC/ED 技术测定前额皮质、纹状体和海马中的 5-HT 及其代谢物 5-羟吲哚乙酸（5-HIAA）水平。通过免疫酶方法分析下丘脑、前额皮质、海马和延髓中的组胺水平。进行行为观察（运动、探索、口腔和刻板行为），并测定多巴胺受体激动剂（SKF 38393、阿扑吗啡）和组胺受体拮抗剂 S(+)氯苯那敏（H(1)）、西咪替丁（H(2)）和噻哌酰胺（H(3)）的作用。我们证实，5,7-DHT 在成年期严重降低了大脑中 5-HT 和 5-HIAA 的含量。所有检查的脑区中的组胺含量也降低了。此外，在 5,7-DHT 损伤的大鼠中，噻哌酰胺对运动和口腔活动的反应发生改变，并且阿扑吗啡诱导的刻板行为加剧。由此，我们得出结论，中枢 5-羟色胺能系统完整调节组胺 H(3)受体拮抗剂对大鼠多巴胺能神经元的影响。
