Research on receptor tyrosine kinase induced by catecholaminergic agonist in rat brain

在儿茶酚胺能激动剂中，甲基苯丙胺（MAP）是日本滥用最多的药物。MAP引起类似于精神分裂症的严重精神病状态（Sato，Numachi，1992）。由于MAP诱导的精神病复发的脆弱性持续很长一段时间，神经功能的持久变化预计是MAP精神病的基础。在MAP处理的动物中观察到的反向耐受现象为MAP精神病以及精神分裂症提供了良好的动物模型（Numachi，1998）。Nishikawa（NCNP，Japan）等人使用RNA任意引物PCR方法发现，通过急性MAP处理，大鼠脑中受体酪氨酸激酶家族之一的rEphA7的mRNA增加。rEphA 7在大脑轴突引导和突触重组中发挥重要作用。为了澄清是否异常突触的形成，相关的反向耐受，诱导MAP通过rEphA7，我们研究了脑表达rEphA7在MAP处理的大鼠使用原位杂交。到目前为止，我们观察到MAP在大鼠前额叶皮层中增加了rEphA6的mRNA。

Among catecholaminergic agonist, methamphetamine (MAP) is the most abused drug in Japan. MAP causes a severe psychotic state which resembles schizophrenia (Sato, Numachi, 1992). Because vulnerability to relapse in MAP-induced psychosis lasts for a long time, enduring changes in neural function is expected to underlie MAP psychosis. Reverse tolerance phenomenon, observed in MAP-treated animals, provides a good animal model for MAP psychosis as well as schizophrenia (Numachi, 1998).By collaboration with Dr. T. Nishikawa (NCNP, Japan) we found that mRNA for rEphA7, one of receptor tyrosine kinases' family, increased in rat brain by acute MAP treatment, using RNA arbitrary-primed PCR method. rEphA7 plays an important role in axonal guidance and synaptic reorganization in brain. To clarify if abnormal synapse formation, related to reverse tolerance, is induced by MAP via rEphA7, we examined brain expression of rEphA7 in brain of MAP-treated rats using in situ hybridization. So far we observed mRNA for rEphA6 is increased in rat prefrontal cortex by MAP.