From Imbalance to Intervention: Neurochemical Alterations in Canine Anxiety and Its Modulation by Repetitive Transcranial Magnetic Stimulation.

OBJECTIVES

Accelerated high-frequency repetitive transcranial magnetic stimulation (aHF-rTMS) is an emerging modality in both human and veterinary medicine. Although previous studies show brain changes and behavioral improvements in healthy and patient dogs, the effects of aHF-rTMS on neurotransmitter levels remain poorly understood. This study aimed to compare monoaminergic metabolite profiles in healthy and anxious dogs, and to evaluate short-term, long-term, and dose-dependent effects of aHF-rTMS on these metabolites.

MATERIALS AND

METHODS

A total of 79 dogs were included, comprising 59 healthy controls and 20 anxious dogs. Cerebrospinal fluid samples were collected to measure dopaminergic (3,4-dihydroxyphenylacetic acid [DOPAC] and homovanillic acid [HVA]) and serotonergic (5-hydroxyindoleacetic acid [5-HIAA]) metabolites before and after various aHF-rTMS protocols with varying dosing and duration. Generalized linear mixed-effects models were used to assess baseline differences and stimulation-induced changes across protocols and timepoints.

RESULTS

Patient dogs consistently showed lower baseline levels of all three metabolites (DOPAC, HVA, and 5-HIAA) than healthy controls, supporting a neurochemical basis for canine anxiety. Furthermore, neuromodulatory effects of aHF-rTMS were selective and dependent on protocol and timing. In healthy dogs, the short-term stimulation increased 5-HIAA whereas longer protocols reduced HVA. In patient dogs, long-term follow-up revealed significant fluctuations in DOPAC, whereas HVA and 5-HIAA remained stable.

CONCLUSIONS

These findings indicate baseline monoaminergic deficits in anxious dogs and support a neurochemical basis for canine anxiety. Moreover, aHF-rTMS induces distinct, state- and duration-dependent neurochemical responses. Overall, this study provides novel insights into the neurobiology of anxious dogs and supports further investigation of aHF-rTMS as a neuromodulatory approach in dogs with translational relevance.