Yamada Ikuko, Iwasaki Tsuneo
Institute of Psychology, University of Tsukuba, Tennodai, 1-1-1, Tsukuba, 305-8572 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2002 Oct;22(5):145-51.
A large body of evidence has shown the involvement of serotonin (5-HT) in anxiety. The administration of serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into adult rats has been shown to produce a prolonged reduction in the content of brain 5-HT along with anxiolytic effects. In this experiment, 5,7-DHT was administrated intraventricularly to neonatal and adult rats. All rats were tested in an elevated plus maze at 30, 50, 70, and 90 days old to evaluate the anxiety level. Adult treatment increased the time spent in open-arm, and decreased the brain 5-HT content in all the regions measured. In contrast, neonatal treatment decreased the time spent in open-arm, and 5-HT contents in these animals did not decrease in the hypothalamus and medulla oblongata. A 5-HT syndrome test was conducted once when the rats were 91 to 97 days old to evaluate the sensitivity of 5-HT recepotors. It was found that 5-HTP (25 mg/kg) produces a severe serotonin syndrome in the adult 5,7-DHT-treated rats, but only a moderate syndrome in the neonatal-treated animals. Significant negative correlation coefficients were obtained between the score of serotonin syndrome and 5-HT content in the hypothalamus, midbrain, medulla oblongata, and cerebellum of the neonatal 5,7-DHT-treated rats. The results suggest that neonatal 5,7-DHT treatment produces an anxiogenic effect in contrast with the anxiolytic effect with adult treatment.
大量证据表明血清素(5-羟色胺,5-HT)与焦虑有关。已证实,向成年大鼠注射血清素能神经毒素5,7-二羟基色胺(5,7-DHT)会使大脑5-HT含量长期降低,并产生抗焦虑作用。在本实验中,向新生大鼠和成年大鼠脑室内注射5,7-DHT。所有大鼠在30、50、70和90日龄时在高架十字迷宫中接受测试,以评估焦虑水平。成年大鼠接受5,7-DHT处理后,在开放臂停留的时间增加,且在所测量的所有脑区中大脑5-HT含量均降低。相比之下,新生大鼠接受5,7-DHT处理后,在开放臂停留的时间减少,且其下丘脑和延髓中的5-HT含量并未降低。当大鼠91至97日龄时进行一次5-HT综合征测试,以评估5-HT受体的敏感性。结果发现,5-羟色氨酸(5-HTP,25 mg/kg)在成年5,7-DHT处理的大鼠中会引发严重的血清素综合征,但在新生大鼠处理组中仅引发中度综合征。在新生5,7-DHT处理的大鼠的下丘脑、中脑、延髓和小脑中,血清素综合征评分与5-HT含量之间获得了显著的负相关系数。结果表明,与成年大鼠接受5,7-DHT处理产生的抗焦虑作用相反,新生大鼠接受5,7-DHT处理会产生致焦虑作用。