Withdrawal-induced c-Fos expression in the rat centromedial amygdala 24 h following a single morphine exposure.
BACKGROUND
An opiate antagonist was found to induce motivational withdrawal signs 24 h or even up to 48 h after a single dose of morphine in rats.


OBJECTIVE
The present study was undertaken to determine whether such a withdrawal state would modify the neuronal activity in the brain.


METHODS
A conditioned place aversion was established following a one-trial paradigm in rats undergoing a single exposure to morphine (10 mg/kg) 24 h prior to naloxone administration (0.5 mg/kg). Subsequently, the expression of the protein product of c-fos gene (c-Fos) following naloxone administration was measured within the extended amygdala.


RESULTS
A significant increase in c-Fos immunoreactivity was seen in the centromedial amygdala (CMA), but not in the bed nucleus of the stria terminalis (BST) and the shell (AcbSh) of the nucleus accumbens (Acb) in rats treated with both morphine and naloxone. Further examination of the distribution of c-Fos-positive neurons along the rostrocaudal axis within CMA showed that the positive neurons distributed throughout this brain area and the caudal level of its central division (the central nucleus of the amygdala, CeA) exhibited the most robust labeling.


CONCLUSIONS
Neuronal activity can be increased by naloxone at a dose that produces conditioned place aversion 24 h after a single morphine exposure. CMA, particularly the caudal level of its central division, was of high sensitivity. The current data also suggest a possible involvement of CMA in negative motivational component of precipitated withdrawal from acute morphine dependence.
Jin
Chunyu
C
Department of Clinical Pharmaceutical Science, Graduate School of Natural Science and Technology, Okayama University, 1-1-1, Tsushima-naka, Okayama, 700-8530, Japan.
Araki
Hiroaki
H
Nagata
Mari
M
Suemaru
Katsuya
K
Shibata
Kazuhiko
K
Kawasaki
Hiromu
H
Hamamura
Takashi
T
Gomita
Yutaka
Y
D000679:Amygdala / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine