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

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&#x2009;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&#x2009;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 (&#x2009;=&#x2009;9), and 5 sham stimulation sessions (&#x2009;=&#x2009;4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1&#x2009;day, 1&#x2009;month, and 3&#x2009;months post stimulation. CSF samples were collected after each scan. RESULTS: Active aHF-rTMS significantly reduced striatal DAT BI 1&#x2009;day post-active stimulation session (&#x2009;<&#x2009;0.01), and the effect lasted to 1&#x2009;month (&#x2009;<&#x2009;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&#x2009;day and up to 1&#x2009;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.