Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs

Yangfeng Xu; Kathelijne Peremans; Sofie Salden; Kurt Audenaert; Andre Dobbeleir; Ann Van Eeckhaut; Dimitri De Bundel; Jimmy H Saunders; Chris Baeken

doi:10.3389/fvets.2023.1154596

Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs

Front Vet Sci. 2023 May 16:10:1154596. doi: 10.3389/fvets.2023.1154596. eCollection 2023.

Authors

Affiliations

¹ Department of Head and Skin, Ghent Experimental Psychiatry (GHEP) Lab, Ghent University, Ghent, Belgium.
² Department of Morphology, Imaging, Orthopedics, Rehabilitation and Nutrition, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
³ Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information (FASC), Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
⁴ Department of Psychiatry, Vrije Universiteit Brussel, Universitair Ziekenhuis Brussel (UZBrussel), Brussels, Belgium.
⁵ Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.

Abstract

Aim: The neurobiological effects of repetitive transcranial magnetic stimulation are believed to run in part through the dopaminergic system. Accelerated high frequency rTMS (aHF-rTMS), a new form of stimuli delivery, is currently being tested for its usefulness in treating human and canine mental disorders. However, the short-and long-term neurobiological effects are still unclear, including the effects on the dopaminergic system. In aHF-rTMS, multiple sessions are delivered within 1 day instead of one session per day, not only to accelerate the time to response but also to increase clinical efficacy. To gain more insight into the neurobiology of aHF-rTMS, we investigated whether applying five sessions in 1 day has direct and/or delayed effects on the dopamine transporter (DAT), and on dopamine metabolites of cerebrospinal fluid (CSF) in beagles.

Materials and methods: Thirteen beagles were randomly divided into two groups: five active stimulation sessions (n = 9), and 5 sham stimulation sessions (n = 4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1 day, 1 month, and 3 months post stimulation. CSF samples were collected after each scan.

Results: Active aHF-rTMS significantly reduced striatal DAT BI 1 day post-active stimulation session (p < 0.01), and the effect lasted to 1 month (p < 0.01). No significant DAT BI change was found in sham group. No significant changes in dopamine metabolites of CSF were found.

Conclusion: Although no significant effects on CSF dopamine metabolites were observed, five sessions of active aHF-rTMS significantly decreased striatal DAT BI after 1 day and up to 1 month post stimulation, indicating immediate and delayed effects on the brain dopaminergic system. Our findings in healthy beagles further substantiate the assumption that (a)HF-rTMS affects the brain dopaminergic system and it may pave the way to apply (a)HF-rTMS treatment in behaviorally disturbed dogs.

Keywords: DaTscan SPECT; aHF-rTMS; behavior disorder; canine model; dopamine; dopamine transporter.