Evidence for a 5-HT6 receptor-mediated control of midbrain 5-HT neurons

Brouard, J

Abstract:: The dorsal raphe nucleus (DRN) contains the majority of 5-hydroxytryptamine (5-HT)-producing neurons, whose firing is influenced by homeostatic feedback pathways. Dysfunction of 5-HT neurons is implicated in the pathophysiology of diseases such as depression. Thus, pathways regulating 5-HT neuron activity represent potential therapeutic targets. Negative feedback pathways influencing 5-HT neurons include 5-HT_1A autoreceptors located in the DRN, and feedback from 5-HT_1A
Expand abstract
Collapse abstract

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Brouard, J. (2016). Evidence for a 5-HT6 receptor-mediated control of midbrain 5-HT neurons [PhD thesis]. University of Oxford.

MLA Style

Brouard, J. Evidence for a 5-HT6 Receptor-Mediated Control of Midbrain 5-HT Neurons. University of Oxford, 2016.

Chicago Style

Brouard, J. 2016. “Evidence for a 5-HT6 Receptor-Mediated Control of Midbrain 5-HT Neurons.” PhD thesis, University of Oxford.
Share
Print

Access Document

Files:: Thesis with corrections JB.pdf

(Preview, pdf, 29.0MB, Terms of use)

Authors

+ Brouard, J More by this author

Division:: MSD
Department:: Pharmacology
Role:: Author

Contributors

+ Sharp, T

Role:: Supervisor

+ H. Lundbeck A/S More from this funder

+ Clarendon Fund More from this funder

DOI:: 10.5287/ora-7rrg4p7v1
Type of award:: DPhil
Level of award:: Doctoral
Awarding institution:: University of Oxford

UUID:: uuid:30a49d17-e976-4cc8-b718-392d725d2ea5
Deposit date:: 2016-10-29

Related item:: Pharmacological evidence for a 5-HT6 receptor modulation of 5-HT neuron firing in vivo
Description:: 5-Hydroxytryptamine (5-HT) neurons in the midbrain dorsal raphe nucleus (DRN) are implicated in the drug treatment and pathophysiology of a wide variety of neuropsychiatric disorders. Accumulating evidence suggests that 5-HT6 receptors may be located and functional in the DRN; therefore, 5-HT6 receptor ligands may have potential as novel modulators of 5-HT neurotransmission. The current study investigated the effect of intravenous (i.v.) administration of the selective 5-HT6 receptor agonist, WAY-181187, and antagonist, SB-399885, on the firing of 5-HT neurons in the DRN in vivo. Extracellular recordings were made in the DRN of anesthetized rats, and single 5-HT neurons were identified on the basis of electrophysiological properties combined with juxtacellular labeling and postmortem immunohistochemical analysis. WAY-181187 (1-4 mg/kg i.v.) caused a dose-dependent increase in 5-HT neuron firing rate. In comparison, SB-399885 (0.125-1 mg/kg i.v.) caused a dose-dependent decrease in 5-HT neuron firing rate, an effect reversed by WAY-181187 (3 mg/kg i.v.). These effects of WAY-181187 and SB-399885 were observed in two separate sets of experiments. In summary, the current data show the modulation of 5-HT neuronal firing by the 5-HT6 ligands WAY-181187 and SB-399885 and are consistent with the presence of 5-HT6 receptor-mediated positive feedback control of 5-HT neurons.

Terms of use

Copyright holder:: Brouard, J

Licence:: Terms and Conditions of Use for Oxford University Research Archive

Views and Downloads

About views and downloads

If you are the owner of this record, you can report an update to it here: Report update to this record

Thesis

Evidence for a 5-HT6 receptor-mediated control of midbrain 5-HT neurons

Actions

Access Document

Authors

Contributors

Terms of use

Views and Downloads

Altmetrics

Dimensions

Thesis

Evidence for a 5-HT6 receptor-mediated control of midbrain 5-HT neurons

Actions

Access Document

Authors

Contributors

Funding

Bibliographic Details

Item Description

Related Items

Terms of use

Metrics

Views and Downloads

Altmetrics

Dimensions