Clinical and experimental studies on oxidative stress-induced impairment and its treatment in schizophrenia

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The effects of acute and chronic administration of methamphetamine (METH) on mRNA levels of synaptotagmin IV (SytIV), synaptic associated protein of 25Kda (SNAP25a) and transcription factor Nurr1 belonging to nuclear receptor superfamily have been investigated in rat brain using in situ hybridization. Pretreatment with SCH23390, but not MK-801, significantly attenuated the acute METH-induced expression levels of SytIV mRNA in the striatum and nucleus accumbens, SNAP 25a mRNA in the striatum and dentate gyros, and Nurr1 mRNA in the in the cerebral cortex, CA1, substantial nigra and ventral segmental area. In the chronic treatment experiment, the SytIV mRNA levels of the group that received chronic treatment with METH followed by a METH challenge were significantly higher in the striatum, nucleus accumbens, somatosensory cortex and dentate gyms than those of the group that received chronic treatment with saline followed by a METH challenge. The SNAP25 a mRNA levels in the striatum and nucleus accumbens, and Nurr1 mRNA levels in the medial frontal cortex, somatosensory cortex and retrosplenial cortex of the group that received chronic treatment with METH followed by a saline challenge were significantly higher than those of the group that received chronic treatment with saline followed by a saline challenge., The effect of pretreatment with a number of neuroleptics on Nurr1 mRNA expression induced by a single administration of phencyclidine, which is an N-methyl-D-aspartate recept or antagonist. Pretreatment with olanzapine and clozapine, but not haloperidol or risperidone, significantly attenuated the increased Nurr1 mRNA levels induced by acute phencyclidine administration in the medial frontal cortex, somatosensory cortex, visual cortex and retrosplenial cortex.