A ROBUST INCREASE IN EXPRESSION OF ARC GENE, AN EFFECTOR IMMEDIATE-EARLY GENE, IN THE RAT-BRAIN AFTER ACUTE AND CHRONIC METHAMPHETAMINE ADMINISTRATION

The effect of acute and chronic administration of methamphetamine (MET H) on the levels of activity-regulated cytoskeleton-associated protein (arc), an effector-immediate early gene, mRNA has been investigated i n rat brain using in situ hybridization. Levels of are mRNAs in the br ain regions examined increased significantly from 0.5-1 h after an acu te METH (4 mg/kg) administration compared with basal levels. The incre ase in are mRNA continued by 3 h, and then subsided to basal levels by 6 h. The degree of increase in are mRNA and the peak time after METH administration varied according to brain area. Are mRNA in cerebral co rtices showed robust increase 1 h after METH administration. In the st riatum and hippocampus, it showed earlier and later increase, respecti vely, and its degree of both was less than in the cortices. Microscopi c examination revealed that the METH-induced are mRNAs in the parietal cortex were enriched in layers IV and VI, and those in the striatum e xisted mainly in the medium-sized neuron. Pretreatment with either 0.5 mg/kg SCH23390 or 0.25 mg/kg MK-801 almost completely blocked the enh anced striatal are mRNA levels induced by acute METH administration, w hereas such pretreatments only partially reduced the effect of METH in the cerebral cortical regions. In the chronic treatment experiment, t he are mRNA levels of the group that received chronic treatment with M ETH followed by a METH challenge showed an increase like seen after ac ute METH administration. Since previous studies proposed that are is o ne of cytoskeleton-associated proteins and is selectively localized in neural dendrites, the results of the present study suggested that are may play an important role in the synaptic plasticity underlying METH -induced adaptational changes including behavioral sensitization. (C) 1998 Elsevier Science B.V. All rights reserved.