Changes in Dopamine Neurotransmission in Rats with the Entorhinal Cortex Lesions.

接下来的实验研究了多巴胺（DA）神经传递的变化与大脑中兴奋性氨基酸传递的减少有关，特别是在精神分裂症患者的内嗅皮层，那里报告了形态学异常。首先，用n -甲基- d -天冬氨酸（NMDA） R1亚基mRNA互补的反义寡核苷酸处理大鼠，研究了n -甲基- d -天冬氨酸（NMDA） R1亚基是谷氨酸受体的一种亚型。原位杂交结果显示，NMDA RI反义处理大鼠脑室周围结构（如内侧纹状体和伏隔核）中NMDA RI亚基mRNA的表达较对照大鼠减少。反义处理大鼠A10 DA神经元放电模式的变异性降低。NMDA R1反义处理对DA、Dl和D2受体mRNA表达水平及酪氨酸羟化酶无显著影响。需要进一步的实验来研究DA D1和D2受体结合的变化，使用受体放射自显影。其次，对喹啉酸损伤大鼠内嗅皮质进行检查。da相关的行为，如探索性运动、甲基苯丙胺诱导的运动活动和刻板印象，正在对内嗅损伤大鼠进行研究。进一步的实验也将在细胞水平上量化DA受体的结合和mRNA的表达。（转到下一页）

Following experiments were undertaken to investigate changes in dopamine (DA) neurotransmission associated with reduced excitatory amino acid transmission in the brain, especially in the entorhinal cortex where morphological abnormalities were reported in patients with schizophrenia. First, rats treated with antisense oligonucleotide complementary to mRNA of N-methyl-D aspartate (NMDA) R1 subunit, one of the subtypes of ionotropic glutamate receptors, were examined. In situ hybridization revealed that NMDA RI subunit mRNA expression was reduced in the periventricular structures such as the medial striatum and nucleus accumbens in the NMDA RI antisense-treated rats compared to the vehicle-treated rats. Variability in the firing pattern of A10 DA neurons was decreased in the antisense-treated rats.NMDA R1 antisense treatment induced no significant changes in mRNA expression levels of DA Dl and D2 receptors, and tyrosine hydroxylase. Further experiments are needed to investigate changes in DA D1 and D2 receptor binding using the receptor autoradiography. Second, rats with quinolinic acid lesions in the entorhinal cortex were examined. DA-related behaviors such as exploratory movements, metamphetamine-induced locomotor activity, and stereotypy are under investigation in the entorhinal- lesioned rats. Further experiments are also going on to quantify the receptor binding and mRNA expressions of DA receptors in cellular level in the entorhinal-lesioned rats.(CONTINUE TO NEXT PAGE)