Fluoxetine inhibits corticotropin-releasing factor (CRF)-induced behavioural responses in rats
Year: 2008
Type: article
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.
Source: Stress
Authors: Christopher A. Lowry, Christopher A. Lowry, Matthew W. Hale, Christopher A. Lowry, Matthew W. Hale, Andrea Plant, Richard J. Windle, Christopher A. Lowry, Matthew W. Hale, Andrea Plant, Richard J. Windle, Nola Shanks, Susan A. Wood, Colin D. Ingram, Christopher A. Lowry, Matthew W. Hale, Andrea Plant, Richard J. Windle, Nola Shanks, Susan A. Wood, Colin D. Ingram, Kenneth J. Renner, Stafford L. Lightman, Cliff H. Summers
Institutions: University of Bristol, University of South Dakota
Language: English
Subfield: Behavioral Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: bronze
Funders: National Science Foundation, Howard Hughes Medical Institute, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, National Institutes of Health, U.S. Public Health Service, National Center for Research Resources, Office of Experimental Program to Stimulate Competitive Research
Awards: South Dakota EPSCoR Advanced Development Program: Infrastructure Improvement Plan, RUI: Hormones Neurotransmitters and Behavior, G3034339878, G5415917556, South Dakota EPSCoR Improvement Plan, G7171933659, G7696971437, NEURAL MECHANISMS OF ADAPTIVE BEHAVIOR, Integrative physiology and behaviour of anxiety: characterisation of an "emotional motor system" and central autonomic control., G9000187273, G968885215
OpenAlex ID: W2066783180