Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress

Currently approved repetitive transcranial magnetic stimulation (rTMS) protocols for the treatment of major depressive disorder (MDD) involve once-daily (weekday) stimulation sessions, with 10 Hz or intermittent theta burst stimulation (iTBS) frequencies, over 4–6 weeks. Recently, accelerated treatm...

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Main Authors: Lauren A. Hennessy, Bhedita J. Seewoo, Liz A. Jaeschke, Leah A. Mackie, Abbey Figliomeni, Yasmin Arena-Foster, Sarah J. Etherington, Sarah A. Dunlop, Paul E. Croarkin, Jennifer Rodger
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Language:English
Published: Elsevier 2022-09-01
Series:NeuroImage: Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666956022000289
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author Lauren A. Hennessy
Bhedita J. Seewoo
Liz A. Jaeschke
Leah A. Mackie
Abbey Figliomeni
Yasmin Arena-Foster
Sarah J. Etherington
Sarah A. Dunlop
Paul E. Croarkin
Jennifer Rodger
author_facet Lauren A. Hennessy
Bhedita J. Seewoo
Liz A. Jaeschke
Leah A. Mackie
Abbey Figliomeni
Yasmin Arena-Foster
Sarah J. Etherington
Sarah A. Dunlop
Paul E. Croarkin
Jennifer Rodger
author_sort Lauren A. Hennessy
collection DOAJ
description Currently approved repetitive transcranial magnetic stimulation (rTMS) protocols for the treatment of major depressive disorder (MDD) involve once-daily (weekday) stimulation sessions, with 10 Hz or intermittent theta burst stimulation (iTBS) frequencies, over 4–6 weeks. Recently, accelerated treatment protocols (multiple daily stimulation sessions for 1–2 weeks) have been increasingly studied to optimize rTMS treatments. Accelerated protocols might confer unique advantages for adolescents and young adults but there are many knowledge gaps related to dosing in this age group. Off-label, clinical practice frequently outpaces solid evidence as rigorous clinical trials require substantial time and resources. Murine models present an opportunity for high throughput dose finding studies to focus subsequent clinical trials in humans. This project investigated the brain and behavioural effects of an accelerated low-intensity rTMS (LI-rTMS) protocol in a young adult rodent model of chronic restraint stress (CRS). Depression and anxiety-related behaviours were induced in young adult male Sprague Dawley rats using the CRS model, followed by the 3-times-daily delivery of 10 Hz LI-rTMS, for two weeks. Behaviour was assessed using the Elevated Plus Maze and Forced Swim Test, and functional, chemical, and structural brain changes measured using magnetic resonance imaging techniques. CRS induced an agitated depression-like phenotype but therapeutic effects from the accelerated protocol were not detected. Our findings suggest that the age of rodents may impact response to CRS and LI-rTMS. Future studies should also examine higher intensities of rTMS and accelerated theta burst protocols.
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spelling doaj-art-596e4d3c71714f0580ccd3b73466ce482025-08-20T03:19:24ZengElsevierNeuroImage: Reports2666-95602022-09-012310010410.1016/j.ynirp.2022.100104Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stressLauren A. Hennessy0Bhedita J. Seewoo1Liz A. Jaeschke2Leah A. Mackie3Abbey Figliomeni4Yasmin Arena-Foster5Sarah J. Etherington6Sarah A. Dunlop7Paul E. Croarkin8Jennifer Rodger9Experimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia; Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Perth, WA, AustraliaExperimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia; Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Perth, WA, Australia; Centre for Microscopy, Characterisation & Analysis, Research Infrastructure Centres, The University of Western Australia, Perth, WA, AustraliaExperimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, AustraliaExperimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, AustraliaBrain Plasticity Group, Perron Institute for Neurological and Translational Science, Perth, WA, Australia; School of Veterinary and Life Sciences, Murdoch University, Perth, WA, AustraliaBrain Plasticity Group, Perron Institute for Neurological and Translational Science, Perth, WA, Australia; School of Human Sciences, The University of Western Australia, Perth, WA, AustraliaMedical, Molecular and Forensic Sciences, Murdoch University, Perth, WA, AustraliaExperimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia; Minderoo Foundation, Perth, WA, AustraliaDepartment of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USAExperimental and Regenerative Neurosciences, School of Biological Sciences, The University of Western Australia, Perth, WA, Australia; Brain Plasticity Group, Perron Institute for Neurological and Translational Science, Perth, WA, Australia; Corresponding author. M317, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009Currently approved repetitive transcranial magnetic stimulation (rTMS) protocols for the treatment of major depressive disorder (MDD) involve once-daily (weekday) stimulation sessions, with 10 Hz or intermittent theta burst stimulation (iTBS) frequencies, over 4–6 weeks. Recently, accelerated treatment protocols (multiple daily stimulation sessions for 1–2 weeks) have been increasingly studied to optimize rTMS treatments. Accelerated protocols might confer unique advantages for adolescents and young adults but there are many knowledge gaps related to dosing in this age group. Off-label, clinical practice frequently outpaces solid evidence as rigorous clinical trials require substantial time and resources. Murine models present an opportunity for high throughput dose finding studies to focus subsequent clinical trials in humans. This project investigated the brain and behavioural effects of an accelerated low-intensity rTMS (LI-rTMS) protocol in a young adult rodent model of chronic restraint stress (CRS). Depression and anxiety-related behaviours were induced in young adult male Sprague Dawley rats using the CRS model, followed by the 3-times-daily delivery of 10 Hz LI-rTMS, for two weeks. Behaviour was assessed using the Elevated Plus Maze and Forced Swim Test, and functional, chemical, and structural brain changes measured using magnetic resonance imaging techniques. CRS induced an agitated depression-like phenotype but therapeutic effects from the accelerated protocol were not detected. Our findings suggest that the age of rodents may impact response to CRS and LI-rTMS. Future studies should also examine higher intensities of rTMS and accelerated theta burst protocols.http://www.sciencedirect.com/science/article/pii/S2666956022000289rTMSChronic stressAnxietyAnimal modelMRIBehaviour
spellingShingle Lauren A. Hennessy
Bhedita J. Seewoo
Liz A. Jaeschke
Leah A. Mackie
Abbey Figliomeni
Yasmin Arena-Foster
Sarah J. Etherington
Sarah A. Dunlop
Paul E. Croarkin
Jennifer Rodger
Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
NeuroImage: Reports
rTMS
Chronic stress
Anxiety
Animal model
MRI
Behaviour
title Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
title_full Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
title_fullStr Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
title_full_unstemmed Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
title_short Accelerated low-intensity rTMS does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
title_sort accelerated low intensity rtms does not rescue anxiety behaviour or abnormal connectivity in young adult rats following chronic restraint stress
topic rTMS
Chronic stress
Anxiety
Animal model
MRI
Behaviour
url http://www.sciencedirect.com/science/article/pii/S2666956022000289
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