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Structural and functional MRI of altered brain development in a novel adolescent rat model of quinpirole-induced compulsive checking behavior

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Title: Structural and functional MRI of altered brain development in a novel adolescent rat model of quinpirole-induced compulsive checking behavior
Authors: Milou Straathof, Erwin L.A. Blezer, Caroline van Heijningen, Christel E. Smeele, Annette van der Toorn, Jan K. Buitelaar, Jeffrey C. Glennon, Willem M. Otte, Rick M. Dijkhuizen, Jan Buitelaar, Saskia de Ruiter, Jilly Naaijen, Sophie Akkermans, Maarten Mennes, Marcel Zwiers, Shahrzad Ilbegi, Leonie Hennissen, Jeffrey Glennon, Ilse van de Vondervoort, Katarzyna Kapusta, NaAAtalia Bielczyk, Houshang Amiri, Martha Havenith, Barbara Franke, Geert Poelmans, Janita Bralten, Tom Heskes, Elena Sokolova, Perry Groot, Steven Williams, DeAAclan Murphy, David Lythgoe, Muriel Bruchhage, Iulia Dud, Bogdan Voinescu, Ralf Dittmann, Tobias Banaschewski, Daniel Brandeis, Konstantin Mechler, Ruth Berg, Isabella Wolf, Alexander Häge, Michael Landauer, Sarah Hohmann, Regina Boecker Schlier, Matthias Ruff, René Mandl, Rick Dijkhuizen, Erwin Blezer, Kajo van der Marel, Pim Pullens, Wouter Mol, Willem Otte, Sarah Durston, VinAAcent Mensen, Bob Oranje, Daphna Joel, John Cryan, Tracey Petryshen, David Pauls, Mai Saito, Angelique Heckman, Sabine Bahn, Ameli Schwalber, Ioana Florea
Source: European Neuropsychopharmacology, 33, pp. 58-70
Publisher Information: Elsevier BV, 2020.
Publication Year: 2020
Subject Terms: Neuroinformatics, Obsessive-Compulsive Disorder, Quinpirole rat model, Quinpirole, Diffusion-weighted MRI, Neurophysiology, Radboud University Medical Center, Adolescents, 150 000 MR Techniques in Brain Function, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Internal Capsule, 130 000 Cognitive Neurology & Memory, Animals, Rats, Long-Evans, Resting-state fMRI, Cognitive Neuroscience - Radboud University Medical Center, Internal Capsule/diagnostic imaging, Behavior, Brain Mapping, Radboudumc 7: Neurodevelopmental disorders DCMN: Donders Center for Medical Neuroscience, Behavior, Animal, Animal, White Matter/diagnostic imaging, Frontostriatal circuitry, Data Science, 220 Statistical Imaging Neuroscience, Long-Evans, Brain, Obsessive-Compulsive Disorder/chemically induced, Nerve Net/diagnostic imaging, Grooming, Magnetic Resonance Imaging, White Matter, Rats, 3. Good health, Obsessive compulsive disorder, Diffusion Magnetic Resonance Imaging, Dopamine Agonists, Human Genetics - Radboud University Medical Center, Sprague-Dawley, Brain/growth & development, Nerve Net, Locomotion
Description: Obsessive-compulsive disorder (OCD) is increasingly considered to be a neurodevelopmental disorder. However, despite insights in neural substrates of OCD in adults, less is known about mechanisms underlying compulsivity during brain development in children and adolescents. Therefore, we developed an adolescent rat model of compulsive checking behavior and investigated developmental changes in structural and functional measures in the frontostriatal circuitry. Five-weeks old Sprague Dawley rats were subcutaneously injected with quinpirole (n = 21) or saline (n = 20) twice a week for five weeks. Each injection was followed by placement in the middle of an open field table, and compulsive behavior was quantified as repeated checking behavior. Anatomical, resting-state functional and diffusion MRI at 4.7T were conducted before the first and after the last quinpirole/saline injection to measure regional volumes, functional connectivity and structural integrity in the brain, respectively. After consecutive quinpirole injections, adolescent rats demonstrated clear checking behavior and repeated travelling between two open-field zones. MRI measurements revealed an increase of regional volumes within the frontostriatal circuits and an increase in fractional anisotropy (FA) in white matter areas during maturation in both experimental groups. Quinpirole-injected rats showed a larger developmental increase in FA values in the internal capsule and forceps minor compared to control rats. Our study points toward a link between development of compulsive behavior and altered white matter maturation in quinpirole-injected adolescent rats, in line with observations in pediatric patients with compulsive phenotypes. This novel animal model provides opportunities to investigate novel treatments and underlying mechanisms for patients with early-onset OCD specifically.
Document Type: Article
Language: English
ISSN: 0924-977X
DOI: 10.1016/j.euroneuro.2020.02.004
Access URL: https://repository.ubn.ru.nl/bitstream/handle/2066/218790/1/218790.pdf
https://pubmed.ncbi.nlm.nih.gov/32151497
https://jglobal.jst.go.jp/detail?JGLOBAL_ID=202002264612796524
http://www.zora.uzh.ch/190456
https://www.sciencedirect.com/science/article/pii/S0924977X20300638
https://pubmed.ncbi.nlm.nih.gov/32151497/
https://www.ncbi.nlm.nih.gov/pubmed/32151497
https://hdl.handle.net/2066/218790
https://repository.ubn.ru.nl//bitstream/handle/2066/218790/218790.pdf
Rights: Elsevier TDM
Accession Number: edsair.doi.dedup.....48d8b3e3b92334a9370f69ce9d830093
Database: OpenAIRE
Description
Abstract:Obsessive-compulsive disorder (OCD) is increasingly considered to be a neurodevelopmental disorder. However, despite insights in neural substrates of OCD in adults, less is known about mechanisms underlying compulsivity during brain development in children and adolescents. Therefore, we developed an adolescent rat model of compulsive checking behavior and investigated developmental changes in structural and functional measures in the frontostriatal circuitry. Five-weeks old Sprague Dawley rats were subcutaneously injected with quinpirole (n = 21) or saline (n = 20) twice a week for five weeks. Each injection was followed by placement in the middle of an open field table, and compulsive behavior was quantified as repeated checking behavior. Anatomical, resting-state functional and diffusion MRI at 4.7T were conducted before the first and after the last quinpirole/saline injection to measure regional volumes, functional connectivity and structural integrity in the brain, respectively. After consecutive quinpirole injections, adolescent rats demonstrated clear checking behavior and repeated travelling between two open-field zones. MRI measurements revealed an increase of regional volumes within the frontostriatal circuits and an increase in fractional anisotropy (FA) in white matter areas during maturation in both experimental groups. Quinpirole-injected rats showed a larger developmental increase in FA values in the internal capsule and forceps minor compared to control rats. Our study points toward a link between development of compulsive behavior and altered white matter maturation in quinpirole-injected adolescent rats, in line with observations in pediatric patients with compulsive phenotypes. This novel animal model provides opportunities to investigate novel treatments and underlying mechanisms for patients with early-onset OCD specifically.
ISSN:0924977X
DOI:10.1016/j.euroneuro.2020.02.004