Alterations in Corticotropin-Releasing Factor and Vasopressin Content in Rat Brain during Morphine Withdrawal: Correlation with Hypothalamic Noradrenergic Activity and Pituitary-Adrenal Response1
- 1Department of Physiology and Pharmacology, Unit of Pharmacology, University School of Medicine (M.V.M., M.L.L.), Murcia, Spain and 2Equip of Neurobiology and Experimental Physiology (M.C.-C., A.B.), INSERM U.308, Nancy, France
Abstract
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 (naı̈ve) 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.
Footnotes
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Send reprint requests to: M.V. Milanés, Unit of Pharmacology, University School of Medicine, Campus de Espinardo, 30100 Murcia, Spain.
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↵1 This work was supported by DGICYT (PB93–1128 and PM96–0095).
- Abbreviations:
- HPA
- hypothalamus-pituitary-adrenal
- CRF
- corticotropin-releasing factor
- AVP
- vasopressin
- NA
- noradrenaline
- PVN
- paraventricular nucleus
- ME
- median eminence
- BNST
- bed nucleus of the stria terminalis
- DMN
- dorsomedial nucleus
- VMN
- ventromedial nucleus
- AN
- arcuate nucleus
- SON
- supraoptic nucleus
- SCN
- suprachiasmatic nucleus
- MHPG
- 3-methoxy-4-hydroxyphenylethylen glycol
- ACTH
- corticotropin
- CNS
- central nervous system
- RIA
- radioimmunoassay
- HPLC
- high-performance liquid chromatography
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- Received April 24, 1997.
- Accepted January 21, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
