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Vol. 285, Issue 2, 700-706, May 1998
Department of Physiology and Pharmacology, Unit of Pharmacology,
University School of Medicine (M.V.M., M.L.L.), Murcia, Spain and
Equip
of Neurobiology and Experimental Physiology (M.C.-C., A.B.), INSERM
U.308, Nancy, France
The modification in the activity of noradrenergic neurons
projecting to the hypothalamus and the pituitary-adrenal response during morphine withdrawal as well its correlation with alterations in
corticotropin-releasing factor (CRF) and vasopressin (AVP) content in
different brain areas was analyzed. Male rats were implanted with
placebo (naïve) or morphine (tolerant/dependent) pellets for 7 days. On day 8, groups of rats received an acute injection of saline
s.c. (control) or naloxone (1 mg/kg s.c.) and were decapitated 30 min
later. After administration of naloxone to tolerant rats (withdrawal)
we found a striking parallelism between an enhanced activity of
hypothalamic noradrenergic neurons and an increased corticosterone
secretion; concomitantly, the CRF but not the AVP content in the
paraventricular nucleus was decreased, which might reflect an increased
release of the peptide. During withdrawal, CRF content also was
decreased in the arcuate nucleus, whereas no changes were found in the
median eminence, dorsomedial, ventromedial nuclei or in the bed nucleus
of the stria terminalis. AVP content levels were not modified in
arcuate nucleus, supraoptic or in the suprachiasmatic nuclei. Present data suggest that a hypothalamic noradrenergic hypersecretion may be
involved in a selectively increased activity of CRF neurons in the
paraventricular nucleus and arcuate nucleus and then in the enhanced
release of corticosterone induced by morphine withdrawal. However, we
did not find any correlation between opioid withdrawal-induced alterations in the pituitary-adrenal axis and AVP modifications.
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