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Functional neuroanatomy of the noradrenergic locus coeruleus: its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans

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Samuels, E., Szabadi, E.·2008·Current Neuropharmacology
DOI 10.2174/157015908785777193PMC PMC2687931
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Abstract

The locus coeruleus (LC), the major noradrenergic nucleus of the brain, gives rise to fibres innervating most structures of the neuraxis. Recent advances in neuroscience have helped to unravel the neuronal circuitry controlling a number of physiological functions in which the LC plays a central role. Two such functions are the regulation of arousal and autonomic activity, which are inseparably linked largely via the involvement of the LC. Alterations in LC activity due to physiological or pharmacological manipulations or pathological processes can lead to distinct patterns of change in arousal and autonomic function. Physiological manipulations considered here include the presentation of noxious or anxiety-provoking stimuli and extremes in ambient temperature. The modification of LC-controlled functions by drug administration is discussed in detail, including drugs which directly modify the activity of LC neurones (e.g., via autoreceptors, storage, reuptake) or have an indirect effect through modulating excitatory or inhibitory inputs. The early vulnerability of the LC to the ageing process and to neurodegenerative disease (Parkinson's and Alzheimer's diseases) is of considerable clinical significance. In general, physiological manipulations and the administration of stimulant drugs, alpha(2)-adrenoceptor antagonists and noradrenaline uptake inhibitors increase LC activity and thus cause heightened arousal and activation of the sympathetic nervous system. In contrast, the administration of sedative drugs, including alpha(2)-adrenoceptor agonists, and pathological changes in LC function in neurodegenerative disorders and ageing reduce LC activity and result in sedation and activation of the parasympathetic nervous system.

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Authors
Samuels, E., & Szabadi, E.
Affiliations
University of Nottingham (GB)
Corresponding author
Szabadi, E.
ORCID
Szabadi, E.
Venue
Current Neuropharmacology
Publisher
Bentham Science Publishers Ltd.
Published
2008-09-01
Volume
6
Issue
3
Pages
254-285
ISSN
1570-159X (ISSN-L)
DOI
10.2174/157015908785777193
PMC
PMC2687931
OpenAlex
W2062503636
Cited by
454
References
17
Citations by year
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FWCI
3.32
Type
journal article
Language
en
Open access
Locations
  • Current Neuropharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
locus coeruleus, noradrenergic system, arousal, autonomic function, sympathetic nervous system, parasympathetic nervous system, norepinephrine reuptake inhibitors, alpha-2 adrenergic agonists, alpha2-adrenoceptor antagonists, stimulants, sedatives, noradrenaline storage, neurodegeneration, Parkinson's disease, Alzheimer's disease, aging, anxiety, noxious stimuli, temperature extremes, neural circuits

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