Evidence That Increased 5-HT Release Evokes Region-Specific Effects on Blood-Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Responses in the Rat Brain

Preece, Mark; Taylor, Matthew; Raley, J; Blamire, Andrew M.; Sharp, Trevor; Sibson, Nr

doi:10.1016/j.neuroscience.2008.12.032

Cited by 24 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has previously been shown that (BOLD) signal is sensitive to changes in 5-HT: the SSRI citalopram was shown to cause region specific changes in MRI signal in human volunteers (McKie et al 2005). In rats, the potent 5-HT releaser fenfluramine also caused region specific changes in brain activation, which were attenuated by the 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA; Preece et al 2009). Furthermore, Downey et al (2010) demonstrated that citalopram phMRI can be used as a Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In this respect, we conducted explorative studies of ex vivo binding assays in various 5-HT-rich brain regions with a radioligand for SERT ([ 123 I]β-CIT (Reneman et al 1999) (experiment B), and phMRI with fluoxetine as an index of 5-HT availability and/or SERT functionality. It has been shown that the blood oxygenation level dependent (BOLD) signal is sensitive for changes in 5-HT itself (Preece et al 2009;McKie et al 2005;Schwarz et al 2007) and SERT function (Downey et al 2010) (experiment C).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment

et al. 2011

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment

et al. 2011

View full text Add to dashboard Cite

show abstract

“…Extracellular 5-HT concentrations reflect changes in 5-HT activity and increases in these concentrations are known to modulate the MRI signal in the rat brain [23]. SSRIs enhance the extracellular concentrations of 5-HT by blocking the 5-HT transporters responsible for reuptake of 5-HT into the presynaptic terminal.…”

Section: Introductionmentioning

confidence: 99%

Increased Response to a 5-HT Challenge After Discontinuation of Chronic Serotonin Uptake Inhibition in the Adult and Adolescent Rat Brain

et al. 2014

View full text Add to dashboard Cite

Little is known about the effects of chronic fluoxetine on 5-HT transmission in the adolescent brain, even though it is acknowledged that the neuroplasticity of the brain during childhood and adolescence might influence the neurobiological mechanisms underlying treatment response. Also, possible ongoing effects on monoamine function following drug discontinuation are unidentified. We therefore examined the chronic effects of fluoxetine on extracellular 5-HT and dopamine concentrations in the medial prefrontal cortex and studied their responsiveness to an acute 5-HT challenge after a one-week washout period, both in adolescent and adult rats. Noradrenaline was measured in adult animals only. Fluoxetine increased 5-HT to 200–300% of control and DA and NA to 150% of control. Although there were no lasting effects of chronic fluoxetine on basal monoamine levels, we observed a clear potentiating effect of previous treatment on the fluoxetine-induced increase in extracellular 5-HT and, to a lesser extent, extracellular DA. No differential effect was found for noradrenaline. Age-at-treatment did not influence these results. So, after cessation of chronic fluoxetine treatment 5-HT responsiveness remains heightened. This may be indicative of the continuing presence of 5-HT receptor desensitization, at least until one week after drug discontinuation in rats. No apparent age-at-treatment effects on extracellular monoamine concentrations in the medial prefrontal cortex were detected, but age-related differences in 5-HT transmission further down-stream or in the recovery processes cannot be ruled out.

show abstract

“…5-HT (releasing agents, selective re-uptake blockers, etc) evoke region-specific changes in blood oxygenation level dependent (BOLD) MRI signals (signal due to a change of the oxygenated/deoxygenated hemoglobin levels occurring during brain activation through an increase of the blood supply to supply the oxygen and glucose to the demanding neurons) providing an index of neurotransmitter function. It has also been shown that these effects can be reversed by treatments that decrease 5-HT availability 16,13,18,7 . In adult rats, BOLD signal changes following acute SSRI administration have been described in several 5-HT related brain regions, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…using a different drug for 5-HT challenge, such as another SSRIs or 5-HT receptor (ant)agonists 16,13,18,7 or even a double challenge in order to reveal underlying mechanisms of drug action 6,19 ; 2. use a different experimental setup, such as a different anesthesia regime, mechanical ventilation, blood-pool contrast agents instead of BOLD 15 , longitudinal studies (animal needs to be kept alive, so no invasive blood pressure/blood gas measurement and/or mechanical ventilation are possible), or even combinations with other (invasive) methods such as recording of neuronal activity using MR-compatible electrodes 10 or PET/SPECT studies 4 ; 3. use different MRI data analysis methods such as the 'p-block' method of McKie 12 or functional connectivity analysis 15 .…”

mentioning

confidence: 99%

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

Klomp

Tremoleda

Schrantee

et al. 2012

JoVE

View full text Add to dashboard Cite

Pharmacological MRI (phMRI) is a new and promising method to study the effects of substances on brain function that can ultimately be used to unravel underlying neurobiological mechanisms behind drug action and neurotransmitter-related disorders, such as depression and ADHD. Like most of the imaging methods (PET, SPECT, CT) it represents a progress in the investigation of brain disorders and the related function of neurotransmitter pathways in a non-invasive way with respect of the overall neuronal connectivity. Moreover it also provides the ideal tool for translation to clinical investigations. MRI, while still behind in molecular imaging strategies compared to PET and SPECT, has the great advantage to have a high spatial resolution and no need for the injection of a contrast-agent or radio-labeled molecules, thereby avoiding the repetitive exposure to ionizing radiations. Functional MRI (fMRI) is extensively used in research and clinical setting, where it is generally combined with a psycho-motor task. phMRI is an adaptation of fMRI enabling the investigation of a specific neurotransmitter system, such as serotonin (5-HT), under physiological or pathological conditions following activation via administration of a specific challenging drug.The aim of the method described here is to assess brain 5-HT function in free-breathing animals. By challenging the 5-HT system while simultaneously acquiring functional MR images over time, the response of the brain to this challenge can be visualized. Several studies in animals have already demonstrated that drug-induced increases in extracellular levels of e.g. 5-HT (releasing agents, selective re-uptake blockers, etc) evoke region-specific changes in blood oxygenation level dependent (BOLD) MRI signals (signal due to a change of the oxygenated/deoxygenated hemoglobin levels occurring during brain activation through an increase of the blood supply to supply the oxygen and glucose to the demanding neurons) providing an index of neurotransmitter function. It has also been shown that these effects can be reversed by treatments that decrease 5-HT availability 16,13,18,7 . In adult rats, BOLD signal changes following acute SSRI administration have been described in several 5-HT related brain regions, i.e. cortical areas, hippocampus, hypothalamus and thalamus 9,16,15 . Stimulation of the 5-HT system and its response to this challenge can be thus used as a measure of its function in both animals and humans 2,11 . Video LinkThe video component of this article can be found at https://www.jove.com/video/3956/ Protocol Preparing animal for in vivo MRI imaging 1. Surgical Cannulation 1. Anesthetize the rat (male Wistar rat, 200-300 g) with isoflurane (5% induction and then reduced to 1.5-2% for maintenance of anesthesia during animal preparation and scanning) given in medical air (21% O 2 , BOC UK). Ensure that the animal is well anesthetized and exhibits no response to a toe pinch. The femoral artery and vein are cannulated for blood gas and blood pressure measurements and a...

show abstract

Evidence That Increased 5-HT Release Evokes Region-Specific Effects on Blood-Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Responses in the Rat Brain

Cited by 24 publications

References 37 publications

Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment

Age-dependent effects of chronic fluoxetine treatment on the serotonergic system one week following treatment

Increased Response to a 5-HT Challenge After Discontinuation of Chronic Serotonin Uptake Inhibition in the Adult and Adolescent Rat Brain

The Use of Pharmacological-challenge fMRI in Pre-clinical Research: Application to the 5-HT System

Contact Info

Product

Resources

About