Chronically administered amphetamine can result in a paranoid psychosi
s that can be re-induced in former amphetamine abusers by psychologica
l stressors. In an attempt to investigate the neurobiological correlat
es of this phenomenon, the present study examined the effects of prior
D-amphetamine sensitization on regional c-fos expression induced by a
psychological stressor. Rats received intermittent footshock in a dis
tinctive environment for 30 min/day for three days. Three days after t
he last fear conditioning session, the animals received injections of
saline or D-amphetamine (4 mg/kg, i.p.) once every second day for 16 d
ays (eight injections in total). After a iii-day drug abstinent period
, the animals were placed in the fear conditioning apparatus but witho
ut footshock. The amphetamine sensitization procedure significantly en
hanced the effects of conditioned fear on c-Sos expression in several
brain regions. These included the cingulate cortex area 3, agranular i
nsular cortex (layers 2 and 3), claustrum, piriform cortex, the shell
region of the nucleus accumbens, medial striatum, ventral lateral sept
um, and CA3 and polymorphic layer of the hippocampal formation. These
results indicate that D-amphetamine sensitization can have long-lastin
g effects on the neural circuitries activated by conditioned stressors
. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.