This study examined if brain pathways in morphine-dependent rats are activa
ted by opioid withdrawal precipitated outside the central nervous system. W
ithdrawal precipitated with a peripherally acting quaternary opioid antagon
ist (naloxone methiodide) increased Fos expression but caused a more restri
cted pattern of neuronal activation than systemic withdrawal (precipitated
with naloxone which enters the brain). There was no effect on locus coerule
us and significantly smaller increases in Fos neurons were produced in most
other areas. However in the ventrolateral medulla (A1/C1 catecholamine neu
rons), nucleus of the solitary tract (A2/C2 catecholamine neurons), lateral
parabrachial nucleus, supramamillary nucleus, bed nucleus of the stria ter
minalis. accumbens core and medial prefrontal cortex no differences in the
withdrawal treatments were detected. We have shown that peripheral opioid w
ithdrawal can affect central nervous system pathways. Crown Copyright (C) 2
001 Published by Elsevier Science Ltd. All rights reserved.