Cited by 213Neurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal PhysiologyOpioid Use Disorder Treatment

Participation of noradrenergic pathways in the expression of opiate withdrawal: biochemical and pharmacological evidence

MALDONADO, RAFAEL·1997·Neuroscience & Biobehavioral Reviews

Abstract

Several lines of biochemical and pharmacological evidence provide support for the involvement of the noradrenergic system in the expression of the somatic symptoms of opiate withdrawal. Early studies reported changes in brain noradrenaline and metabolite levels during opiate dependence. The significance of these changes has been clarified in recent microdialysis studies indicating that acute morphine decreases the extraneuronal levels of noradrenaline, whereas an increase in release of the neurotransmitter occurs during opiate withdrawal in several brain areas. Changes in the sensitivity and density of alpha 2- and beta-adrenoceptors have also been reported, probably as a consequence of the decreased presynaptic noradrenergic activity induced during morphine dependence. In addition, the administration of alpha 2-agonists, such as clonidine, or beta-antagonists, such as propranolol, has been reported to attenuate some manifestations of opiate withdrawal. The noradrenergic structure mediating the expression of opioid abstinence seems to be the locus coeruleus. However, the activation of the locus coeruleus during morphine withdrawal seems to be primarily due to the afferent projections containing excitatory amino acids and derived from the nucleus paragigantocellularis, although intrinsic modifications, consisting of an up-regulation of the cAMP pathway, seem also to be involved in this activation. The participation of the mesolimbic dopaminergic system in opiate dependence and its relation with the changes produced in the noradrenergic system are also discussed.

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Crossref · 10.1016/0149-7634(95)00061-5

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  • Norepinephrine activation has long been hypothesized to be involved in opioid withdrawal in animals and in humans.

    “Norepinephrine activation has long been hypothesized to be involved in opioid withdrawal in animals, based on neurobiological measures and the pharmacology of withdrawal (Maldonado, 1997), and in humans, based largely on pharmacological studies of opioid withdrawal (Gold et al., 1978;Harris and Gewirtz, 2005).”

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Authors
MALDONADO, R.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
MALDONADO, RAFAEL
Venue
Neuroscience & Biobehavioral Reviews
Publisher
Elsevier BV
Published
1997-01
Volume
21
Issue
1
Pages
91-104
ISSN
0149-7634 (ISSN-L)
OpenAlex
W1991473840
Cited by
213
References
142
Citations by year
2026: 5 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 8 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 8 · 2014: 3 · 2013: 11 · 2012: 7
FWCI
0.72
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience & Biobehavioral Reviews (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
Keywords
opioid withdrawal, noradrenergic system, locus coeruleus, morphine dependence, norepinephrine, alpha2-adrenoceptors, beta-adrenergic receptors, clonidine, propranolol, nucleus paragigantocellularis, excitatory amino acids, cAMP pathway, mesolimbic dopamine system
MeSH terms
Adrenergic Fibers, Animals, Narcotics, Neural Pathways, Substance Withdrawal Syndrome

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