Cited by 213Neuropeptides and Animal PhysiologyStress Responses and CortisolNeurotransmitter Receptor Influence on Behavior

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Corticotropin-Releasing Factor Increases In Vitro Firing Rates of Serotonergic Neurons in the Rat Dorsal Raphe Nucleus: Evidence for Activation of a Topographically Organized Mesolimbocortical Serotonergic System

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Lowry, Christopher A., Rodda, Joanne E., Lightman, Stafford L., Ingram, Colin D.·2000·The Journal of Neuroscience

DOI 10.1523/jneurosci.20-20-07728.2000PMC PMC6772886

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Abstract

In vivo studies suggest that the stress-related neuropeptide corticotropin-releasing factor (CRF) modulates serotonergic neurotransmission. To investigate the underlying mechanisms for this interaction, the present study examined the effects of CRF in vitro on dorsal raphe neurons that displayed electrophysiological and pharmacological properties consistent with a serotonergic phenotype. In the presence of either 1 or 2 mm Ca(2+), perfusion of ovine CRF or rat/human CRF rapidly and reversibly increased firing rates of a subpopulation (19 of 70, 27%) of serotonergic neurons predominantly located in the ventral portion of the dorsal raphe nucleus. For a given responsive neuron, the excitatory effects of CRF were reproducible, and there was no tachyphylaxis. Excitatory effects were dose-dependent (over the range of 0.1-1.6 micrometer) and were completely absent after exposure to the competitive CRF receptor antagonists alpha-helical CRF(9-41) or rat/human [d-Phe(12), Nle(21, 38), alpha-Me-Leu(37)]-CRF(12-41). Both the proportion of responsive neurons and the magnitude of excitatory responses to CRF in the ventral portion of the caudal dorsal raphe nucleus were markedly potentiated in slices prepared from animals previously exposed to isolation and daily restraint stress for 5 d. Immunohistochemical staining of the recorded slices revealed close associations between CRF-immunoreactive varicose axons and tryptophan hydroxylase-immunoreactive neurons in the area of the recordings, providing anatomical evidence for potential direct actions of CRF on serotonergic neurons. The electrophysiological properties and the distribution of responsive neurons within the dorsal raphe nucleus are consistent with the hypothesis that endogenous CRF activates a topographically organized mesolimbocortical serotonergic system.

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Lowry, 1999, Corticotropin-releasing factor (CRF) increases in vitro firing rates of serotonergic neurones in the rat dorsal raphe nucleus: evidence for selective activation of a topographically organised mesolimbocortical serotonergic system., Soc Neurosci Abstr, 25, 75

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“The source of DRN CRF is currently unknown; however, multiple studies have shown that DRN 5-HT neurons respond to CRF (Kirby et al., 2000; Lowry et al., 2000; Price et al.,1998; Price and Lucki, 2001), andhave suggested that the source of raphe CRFmaycome from CRF-rich regions like the BNST (see…”
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Authors: Lowry, C. A., Rodda, J. E., Lightman, S. L., & Ingram, C. D.
Affiliations: University of Bristol (GB)
ORCID: Lowry, Christopher A.
Rodda, Joanne E.
Lightman, Stafford L.
Ingram, Colin D.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2000-10-15
Volume: 20
Issue: 20
Pages: 7728-7736
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.20-20-07728.2000
PMC: PMC6772886
OpenAlex: W2109594449
Cited by: 211
References: 113
Citations by year: 2026: 2 · 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 5 · 2015: 7 · 2014: 8 · 2013: 5 · 2012: 8
FWCI: 5.00
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Newcastle University ePrints (Newcastle Univesity)
Funders: Wellcome Trust (045843/Z/95/Z)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: corticotropin-releasing factor, dorsal raphe nucleus, serotonergic neurons, neuronal firing rate, CRF receptor antagonists, tryptophan hydroxylase, stress, isolation stress, restraint stress, topographic organization
MeSH terms: Action Potentials, Animals, Axons, Calcium, Corticotropin-Releasing Hormone, Dose-Response Relationship, Drug, Immunohistochemistry, Male, Microelectrodes, Synaptic Transmission, Neurons, Raphe Nuclei, Reaction Time, Restraint, Physical, Serotonin, Stress, Physiological, Tryptophan Hydroxylase, Rats, Wistar, Serotonin Receptor Agonists, Rats, In Vitro Techniques

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Corticotropin-Releasing Factor Increases In Vitro Firing Rates of Serotonergic Neurons in the Rat Dorsal Raphe Nucleus: Evidence for Activation of a Topographically Organized Mesolimbocortical Serotonergic System

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