M. Kodama et al., A ROBUST INCREASE IN EXPRESSION OF ARC GENE, AN EFFECTOR IMMEDIATE-EARLY GENE, IN THE RAT-BRAIN AFTER ACUTE AND CHRONIC METHAMPHETAMINE ADMINISTRATION, Brain research, 796(1-2), 1998, pp. 273-283
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.