Effects of the β3-adrenoceptor (Adrb3) agonist SR58611A (amibegron) on serotonergic and noradrenergic transmission in the rodent: Relevance to its antidepressant/anxiolytic-like profile
Abstract
SR58611A is a selective beta(3)-adrenoceptor (Adrb3) agonist which has demonstrated antidepressant and anxiolytic properties in rodents. The present study confirmed the detection of Adrb3 mRNA transcript in rodent brain sub-regions and evaluated the effect of SR58611A on serotonergic and noradrenergic transmission in rats and mice in an attempt to elucidate the mechanism(s) underlying these properties. SR58611A (3 and 10 mg/kg, p.o.) increased the synthesis of 5-HT and tryptophan (Trp) levels in several rodent brain areas (cortex, hippocampus, hypothalamus, striatum). Moreover, SR58611A (10 mg/kg, p.o.) increased the release of 5-HT assessed by in vivo microdialysis in rat prefrontal cortex. Systemic (3 mg/kg, i.v.) or chronic administration of SR58611A (10 mg/kg, p.o.), in contrast to fluoxetine (15 mg/kg, p.o.), did not modify the activity of serotonergic neurons in the rat dorsal raphe nucleus. The increase in 5-HT synthesis induced by SR58611A was not observed in Adrb3s knockout mice, suggesting a selective involvement of Adrb3s in this effect. SR58611A (3 and 10 mg/kg, p.o.) did not modify norepinephrine synthesis and metabolism but increased its release in rat brain. Repeated administration of SR58611A (10 mg/kg, p.o.) did not modify basal norepinephrine release in rat prefrontal cortex whereas it prevented its tail-pinch stress-induced enhancement similarly to reboxetine (15 mg/kg, p.o.). Finally SR58611A increased the firing rate of noradrenergic neurons in the rat lo…
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ADRB3 is the key mediator for the stimulatory effects of catecholamines on WAT lipolysis and BAT thermogenesis.
“ADRB3 is the key mediator for the stimulatory effects of catecholamines on WAT lipolysis and BAT thermogenesis (Claustre et al, 2008; Jiang et al, 2017).”
From Exercise‐induced α‐ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1‐dependent adrenal activation (2020) · cites this paper as Claustre et al, 2008
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EFFECTS OF LEPTIN ON ESTABLISHED GLIOBLASTOMA CELL LINES
Cook, N. (2014)
- Authors
- Claustre, Y., Leonetti, M., Santucci, V., Bougault, I., Desvignes, C., Rouquier, L., Aubin, N., Keane, P., Busch, S., Chen, Y., Palejwala, V., Tocci, M., Yamdagni, P., Didier, M., Avenet, P., Le Fur, G., Oury-Donat, F., Scatton, B., & Steinberg, R.
- Affiliations
- Sanofi (France) (FR)
- Sanofi (United States) (US)
- Corresponding author
- Claustre, Y.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 156
- Issue
- 2
- Pages
- 353-364
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W1984507461
- Cited by
- 59
- References
- 52
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 7 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 3 · 2014: 3 · 2013: 6 · 2012: 2
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- beta3-adrenergic agonists, antidepressant-like effects, anxiolytic-like effects, serotonergic neurotransmission, noradrenergic neurotransmission, tryptophan, noradrenaline release, dorsal raphe nucleus, locus coeruleus
- MeSH terms
- Reboxetine, Action Potentials, Adrenergic beta-Agonists, Analysis of Variance, Animals, Brain, Dose-Response Relationship, Drug, Drug Administration Routes, Drug Interactions, Fluoxetine, Male, Morpholines, Motor Activity, Neurons, Norepinephrine, Serotonin, Tetrahydronaphthalenes, Tryptophan, Selective Serotonin Reuptake Inhibitors, Microdialysis, Receptors, Adrenergic, beta-2, Adrenergic Uptake Inhibitors, Mice, Rats, Adrenergic beta-2 Receptor Agonists
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