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

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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.