High-frequency transcranial magnetic stimulation decreases dorsal striatum dopamine D2 receptors in a rat model of depression

Major Depressive Disorder (MDD) is a prevalent chronic mental illness worldwide. Antidepressants are a fundamental part of their treatment, being effective in 60-70 % of patients. Alternative therapies, such as repetitive transcranial magnetic stimulation (rTMS), have also been proposed for modulating cortical neuronal activity and activating circuits associated with the stimulated area. Dopamine is one of the principal neurotransmitters in the nigrostriatal pathway. Changes in dopaminergic transmission through the mesolimbic pathway have been identified as part of the pathophysiology of depression; however, there are only a small number of studies examining the relationship between the nigrostriatal pathway and depression. This study aims to describe the effect of rTMS on the dorsal striatum and prefrontal cortex in a rat model of depression. Behaviors associated with the developed depression and anxiety were assessed through a test battery consisting of sucrose preference, forced swimming, open field, and elevated plus maze.The10 Hz rTMS was applied daily for 15 days, and behavioral tests were re-evaluated. The brains were obtained and analyzed through immunofluorescence labeling of tyrosine hydroxylase and dopamine D2 receptors. It was observed that rTMS reduces depression-like behaviors.Dopamine D2 receptor density decreased in the dorsal striatum and prefrontal cortex of rats that received treatment compared to those with sham stimulation and untreated animals. These results indicate that rTMS affects not only the stimulated region but also influences the dorsal striatum. This finding might contribute to improving the anti-depressive behavior observed in the chronic unpredictable mild stress rat model.