Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5‐hydroxtryptamine system

Haddjeri, Nasser; De Montigny, Claude; Blier, Pierre

doi:10.1038/sj.bjp.0700968

Cited by 164Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuroscience of respiration and sleep

Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5‐hydroxtryptamine system

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Haddjeri, Nasser, De Montigny, Claude, Blier, Pierre·1997·British Journal of Pharmacology

DOI 10.1038/sj.bjp.0700968PMC PMC1564533

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Abstract

The aim of the present study was to investigate the putative modulation of locus coeruleus (LC) noradrenergic (NA) neurones by the 5‐hydroxytryptaminergic (5‐HT) system by use of in vivo extracellular unitary recordings and microiontophoresis in anaesthetized rats. To this end, the potent and selective 5‐HT 1A receptor antagonist WAY 100635 (N‐{2‐[4(2‐methoxyphenyl)‐1‐piperazinyl]ethyl}‐N‐(2‐pyridinyl)cyclohexanecarboxamide trihydroxychloride) was used. In the dorsal hippocampus, both local (by microiontophoresis, 20 nA) and systemic (100 μg kg−1, i.v.) administration of WAY 100635 antagonized the suppressant effect of microiontophorectically‐applied 5‐HT on the firing activity of CA 3 pyramidal neurones, indicating its antagonistic effect on postsynaptic 5‐HT 1A receptors. WAY 100635 and 5‐HT failed to modify the spontaneous firing activity of LC NA neurones when applied by microiontophoresis. However, the intravenous injection of WAY 100635 (100 μg kg−1) readily suppressed the spontaneous firing activity of LC NA neurones. The lesion of 5‐HT neurones with the neurotoxin 5,7‐dihydroxytryptamine increased the spontaneous firing activity of LC NA neurones and abolished the suppressant effect of WAY 100635 on the firing activity of LC NA neurones. In order to determine the nature of the 5‐HT receptor subtypes mediating the suppressant effect of WAY 100635 on NA neurone firing activity, several 5‐HT receptor antagonists were used. The selective 5‐HT 3 receptor antagonist BRL 46470A (10 and 100 μg kg−1, i.v.), the 5‐HT 1D receptor antagonist GR 127935 (100 μg kg−1, i.v.) and the 5‐HT 1A/1B receptor antagonist (−)‐pindolol (15 mg kg−1, i.p.) did not prevent the suppressant effect of WAY 100635 on the firing activity of LC NA neurones. However, the suppressant effect of WAY 100635 was prevented by the non‐selective 5‐HT receptor antagonists spiperone (1 mg kg−1, i.v.) and metergoline (1 mg kg−1, i.v.), by the 5‐HT 2 receptor antagonist ritanserin (500 μg kg−1, i.v.). It was also prevented by the 5‐HT 1A receptor/α 1D‐adrenoceptor antagonist BMY 7378 (1 mg kg−1, i.v.) and by the α 1‐adrenoceptor antagonist prazosin (100 μg kg−1, i.v.). These data support the notion that the 5‐HT system tonically modulates NA neurotransmission since the lesion of 5‐HT neurones enhanced the LC NA neurones firing activity and the suppressant effect of WAY 100635 on the firing activity of NA neurones was abolished by this lesion. However, the location of the 5‐HT 1A receptors involved in this complex circuitry remains to be elucidated. It is concluded that the suppressant effect of WAY 100635 on the firing activity of LC NA neurones is due to an enhancement of the function of 5‐HT neurones via a presynaptic 5‐HT 1A receptor. In contrast, the postsynaptic 5‐HT receptor mediating this effect of WAY 100635 on NA neurones appears to be of the 5‐HT 2A subtype. British Journal of Pharmacology (1997) 120, 865–875; doi:10.1038/sj.bjp.0700968

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Long-term use of SSRIs can increase 5-HT transmission in the LC, thereby increasing the release of GABA to exert inhibitory effects on NA neurons.
“Third, long-term use of SSRIs can increase 5-HT transmission in the LC, 362 thereby increasing the release of GABA to exert inhibitory effects on NA neurons. 363”
From Major depressive disorder: hypothesis, mechanism, prevention and treatment (2024) · cites this paper as [362]
The Discussion (page unavailable) reports tonic inhibition of rat LC noradrenergic neurons by the 5-HT system. The Introduction (page unavailable) describes increased GABA inhibitory input as a proposed explanation for the effect of a 5-HT2 agonist. Neither passage establishes that long-term SSRI use increases 5-HT transmission in the LC or GABA release. (LLM, conf=0.86)
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Authors: Haddjeri, N., De Montigny, C., & Blier, P.
Affiliations: McGill University (CA)
Corresponding author: Haddjeri, Nasser
ORCID: Haddjeri, Nasser
Blier, Pierre
Venue: British Journal of Pharmacology
Publisher: Wiley
Published: 1997-02
Volume: 120
Issue: 5
Pages: 865-875
ISSN: 0007-1188 (ISSN-L)
1476-5381
DOI: 10.1038/sj.bjp.0700968
PMC: PMC1564533
OpenAlex: W1965641144
Cited by: 164
References: 76
Citations by year: 2026: 4 · 2025: 4 · 2024: 4 · 2023: 4 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 7 · 2016: 2 · 2015: 3 · 2014: 10 · 2013: 4 · 2012: 7
FWCI: 3.94
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4385 d)
Locations: British Journal of Pharmacology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Medical Research Council Canada
Medical Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroscience of respiration and sleep
Keywords: locus coeruleus, noradrenergic neurons, serotonin, WAY-100635, 5-HT1A receptor, neuronal firing, CA3 pyramidal cells, dorsal hippocampus, 5,7-dihydroxytryptamine lesion, 5-HT receptor subtypes
MeSH terms: Animals, Hippocampus, Iontophoresis, Locus Coeruleus, Male, Neurons, Norepinephrine, Piperazines, Pyridines, Serotonin, Serotonin Antagonists, Rats, Sprague-Dawley, Rats

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Modulation of the firing activity of noradrenergic neurones in the rat locus coeruleus by the 5‐hydroxtryptamine system

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