Modulation of noradrenergic neuronal firing by selective serotonin reuptake blockers
Open accessAbstract
Using in vivo extracellular unitary recording, the effect of short term (2‐day) and long‐term (21‐day) administration of the selective 5‐HT reuptake inhibitor (SSRI) paroxetine (10 mg kg−1 day−1, s.c. using osmotic minipumps) was examined on the spontaneous firing activity of locus coeruleus noradrenergic neurons. Long‐term but not short‐term treatment significantly decreased firing activity. Thus, it appears that enhancing 5‐HT neurotransmission by sustained SSRI administration leads to a reduction of the firing rate of noradrenergic neurons. The SSRI paroxetine therefore alters the activity of noradrenergic neurons with a delay that is consistent with its therapeutic action in depression and panic disorder. British Journal of Pharmacology (1999) 126, 568–571; doi:10.1038/sj.bjp.0702343
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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 [363]
The Discussion (page unavailable) says that long-term SSRI treatment increases 5-HT release and proposes that this inhibits locus coeruleus noradrenergic neurons; the study observed reduced firing after 21 days of paroxetine treatment in rats. It proposes increased activation of 5-HT2A receptors, not increased GABA release, so the claimed GABA mechanism is unsupported by our copy. (LLM, conf=0.88)
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“363 Fourth, long-term use of SSRIs is associated with neuroplasticity and neurogenesis in certain brain regions.”
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- Authors
- Szabo, S. T., De Montigny, C., & Blier, P.
- Affiliations
- McGill University (CA)
- Corresponding author
- Szabo, Steven T
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 1999-02
- Volume
- 126
- Issue
- 3
- Pages
- 568-571
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC1565850
- OpenAlex
- W2065033597
- Cited by
- 114
- References
- 21
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 4 · 2012: 7
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- paroxetine, selective serotonin reuptake inhibitors, noradrenergic neurons, locus coeruleus, spontaneous firing rate, serotonergic neurotransmission, long-term drug effects, depression, panic disorder, noradrenergic modulation
- MeSH terms
- Animals, Evoked Potentials, Locus Coeruleus, Male, Neurons, Citalopram, Rats, Sprague-Dawley, Selective Serotonin Reuptake Inhibitors, Paroxetine, Rats
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