Research article summary (published 30 Dec 2008):

Fluoxetine inhibits corticotropin-releasing factor (CRF)-induced behavioural responses in rats.

Full Abstract

Corticotropin-releasing factor (CRF) is a potent neuromodulator of stress-related behaviour but the neural mechanisms underlying these effects are not clear. Studies were designed to test the hypothesis that CRF-induced behavioural arousal involves interactions with brainstem serotonergic systems. To examine interactions between CRF and serotonergic systems in the regulation of behaviour, CRF (1 microg, intracerebroventricular (i.c.v.)) or vehicle was infused in the presence or absence of the selective serotonin re-uptake inhibitor fluoxetine (0, 0.1, 1 or 10 mg/kg, intravenous (i.v.)). Fluoxetine was used at these doses because it is known to decrease serotonin cell firing rates while increasing extracellular serotonin concentrations in select forebrain regions. We then measured behavioural, neurochemical and endocrine responses. CRF increased locomotion and spontaneous non-ambulatory motor activity (SNAMA) in the home cages. Fluoxetine decreased tissue 5-hydroxyindoleacetic acid concentrations, a measure of serotonin metabolism, in specific limbic brain regions of CRF-treated rats (nucleus accumbens shell region, entorhinal cortex, central nucleus of the amygdala). Furthermore, fluoxetine inhibited CRF-induced SNAMA. CRF and fluoxetine independently increased plasma corticosterone concentrations, but the responses had distinct temporal profiles. Overall, these data are consistent with the hypothesis that CRF-induced facilitation of behavioural activity is dependent on brainstem serotonergic systems. Therefore, fluoxetine may attenuate or alleviate some behavioural responses to stress by interfering with CRF-induced responses.

Author information

Author/s: Lowry, Christopher A (CA); Hale, Matthew W (MW); Plant, Andrea (A); Windle, Richard J (RJ); Shanks, Nola (N); Wood, Susan A (SA); Ingram, Colin D (CD); Renner, Kenneth J (KJ); Lightman, Stafford L (SL); Summers, Cliff H (CH);

Affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol, UK.

Grants: 040196/Z/93/Z (Agency:Wellcome Trust) ; 045843/Z/95/Z (Agency:Wellcome Trust) ; NICHD-1-T32-HDO 7303-01A1 (Agency:PHS HHS) ; P20 RR15567 (Agency:NCRR NIH HHS) ; RCDF 068558/Z/02/Z (Agency:Wellcome Trust)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Stress (Amsterdam, Netherlands) (Stress), published in England. (Language: eng)

Reference: 2009-; vol 12 (issue 3) : pp 225-39

Dates: Created 2009/04/29; Completed 2009/08/03;

PMID: 18951247, status: MEDLINE (last retrieved date: 8/21/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Animals Arousal - drug effects Behavior, Animal - drug effects Corticosterone - blood Corticotropin-Releasing Hormone - antagonists & inhibitors; physiology Fluoxetine - administration & dosage; pharmacology Hydroxyindoleacetic Acid - metabolism Injections, Intraventricular

Injections, Intraventricular Locomotion - drug effects Male Motor Activity - drug effects Prosencephalon - drug effects; metabolism Rats Rats, Wistar Serotonin - metabolism

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Corticosterone (50-22-6) ; Serotonin (50-67-9) ; Hydroxyindoleacetic Acid (54-16-0) ; Fluoxetine (54910-89-3) ; Corticotropin-Releasing Hormone (9015-71-8)

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