Department of Medicine, Division of Neurology, University of British Columbia, Vancouver, British Columbia, Canada.
École de Kinésiologie et des Sciences de l'activité Physique, Faculté de médecine, Université de Montréal, Montreal, QC, Canada; Centre de Recherche de l'institut Universitaire de Gériatrie de Montréal, Montreal, QC, Canada.
Exp Neurol. 2022 Aug;354:114106. doi: 10.1016/j.expneurol.2022.114106. Epub 2022 May 6.
Dopamine modulation is thought to underpin some of the therapeutic effects associated with repetitive transcranial magnetic stimulation (rTMS). However, patient studies have failed to demonstrate consistent changes in the dopamine system in vivo after a therapeutic course of rTMS. Here, we evaluated acute and chronic changes in striatal dopamine release elicited by a clinically relevant course of theta burst (TBS) or sham stimulation using [C]raclopride in healthy non-human primates (n = 11). Subjects were scanned immediately after the first session of TBS and the day after a 3 week course of daily TBS delivery. After experiment completion, animals were euthanized, and immunofluorescence staining was carried out using antibodies targeting D receptors (DR). Continuous TBS (cTBS, an inhibitory form of rTMS) over the left primary motor cortex acutely decreased dopamine release bilaterally in the putamen. However, no significant changes in dopamine receptors nor DR immunoreactivity were noted 24 h after the last stimulation, while a decrease in cortical excitability, as measured by an increase in resting motor threshold, could still be quantified. On the opposite, intermittent TBS (iTBS, an excitatory form of rTMS) did not affect dopamine release, acutely or chronically, DR immunoreactivity or cortical excitability. These findings suggest that the long-term therapeutic effects of TBS might be facilitated through the modulation of different neurotransmission systems beyond the dopamine system. However, given the small sample size, these results should be interpreted with caution.
多巴胺调节被认为是重复经颅磁刺激（rTMS）治疗效果的基础之一。然而，患者研究未能证明 rTMS 治疗疗程后体内多巴胺系统有一致的变化。在这里，我们使用 [C]raclopride 在健康非人类灵长类动物（n=11）中评估了临床相关的 theta 爆发（TBS）或假刺激疗程对纹状体多巴胺释放的急性和慢性变化。在 TBS 的第一个疗程后，立即对受试者进行扫描，并在 3 周每日 TBS 疗程后的第二天进行扫描。实验完成后，对动物进行安乐死，并使用针对 D 受体（DR）的抗体进行免疫荧光染色。左初级运动皮层的连续 TBS（cTBS，rTMS 的抑制形式）急性双侧降低了纹状体的多巴胺释放。然而，最后一次刺激 24 小时后，多巴胺受体或 DR 免疫反应性没有明显变化，而皮质兴奋性的降低，即静息运动阈值的增加，仍然可以定量。相反，间歇性 TBS（iTBS，rTMS 的兴奋形式）无论是急性还是慢性，均未影响多巴胺释放、DR 免疫反应性或皮质兴奋性。这些发现表明，TBS 的长期治疗效果可能通过调节除多巴胺系统以外的不同神经递质系统来实现。然而，鉴于样本量较小，这些结果应谨慎解释。
