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

本研究旨在探讨多巴胺（DA）神经传递的变化与脑内兴奋性氨基酸传递减少的关系，特别是精神分裂症患者内嗅皮层的形态学异常。首先，用与N-甲基-D天冬氨酸（NMDA）R1亚基（离子型谷氨酸受体亚型之一）的mRNA互补的反义寡核苷酸处理大鼠，进行了检查。原位杂交结果显示，NMDA RI反义处理组大鼠的侧脑室周围结构，如内侧纹状体和脑桥核，NMDA RI亚基mRNA表达较对照组减少。NMDA R1反义处理后，DA D1、D2受体和酪氨酸羟化酶的mRNA表达水平无明显变化。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。第二，检查了内嗅皮质中喹啉酸损伤的大鼠。DA相关的行为，如探索性运动，甲基苯丙胺诱导的运动活动，和刻板行为正在研究中的内嗅损伤大鼠。进一步的实验还将在细胞水平上定量测定内鼻损伤大鼠DA受体的受体结合和mRNA表达。（继续到下一页）

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)