Functional Neuromodulation and Novel Therapeutics Laboratory, Asia Pacific Centre for Neuromodulation, Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Department of Neurologic Surgery, Neural Engineering Laboratories, Mayo Clinic, Rochester, Minnesota, USA.
Bipolar Disord. 2024 Jun;26(4):376-387. doi: 10.1111/bdi.13423. Epub 2024 Apr 1.
Treatment of refractory bipolar disorder (BD) is extremely challenging. Deep brain stimulation (DBS) holds promise as an effective treatment intervention. However, we still understand very little about the mechanisms of DBS and its application on BD.
The present study aimed to investigate the behavioural and neurochemical effects of ventral tegmental area (VTA) DBS in an animal model of mania induced by methamphetamine (m-amph).
Wistar rats were given 14 days of m-amph injections, and on the last day, animals were submitted to 20 min of VTA DBS in two different patterns: intermittent low-frequency stimulation (LFS) or continuous high-frequency stimulation (HFS). Immediately after DBS, manic-like behaviour and nucleus accumbens (NAc) phasic dopamine (DA) release were evaluated in different groups of animals through open-field tests and fast-scan cyclic voltammetry. Levels of NAc dopaminergic markers were evaluated by immunohistochemistry.
M-amph induced hyperlocomotion in the animals and both DBS parameters reversed this alteration. M-amph increased DA reuptake time post-sham compared to baseline levels, and both LFS and HFS were able to block this alteration. LFS was also able to reduce phasic DA release when compared to baseline. LFS was able to increase dopamine transporter (DAT) expression in the NAc.
These results demonstrate that both VTA LFS and HFS DBS exert anti-manic effects and modulation of DA dynamics in the NAc. More specifically the increase in DA reuptake driven by increased DAT expression may serve as a potential mechanism by which VTA DBS exerts its anti-manic effects.
治疗难治性双相情感障碍（BD）极具挑战性。深部脑刺激（DBS）作为一种有效的治疗干预手段具有很大的潜力。然而，我们对 DBS 的作用机制及其在 BD 中的应用仍然知之甚少。
本研究旨在探讨腹侧被盖区（VTA）刺激在 methamphetamine（m-amph）诱导的躁狂动物模型中的行为和神经化学效应。
Wistar 大鼠接受 14 天的 m-amph 注射，最后一天，动物接受两种不同模式的 VTA DBS：间歇性低频刺激（LFS）或连续高频刺激（HFS）。DBS 后立即通过旷场试验和快速扫描循环伏安法评估不同组动物的躁狂样行为和伏隔核（NAc）相位多巴胺（DA）释放。通过免疫组织化学评估 NAc 多巴胺能标志物的水平。
m-amph 诱导动物出现过度活跃，两种 DBS 参数均逆转了这种改变。与基线相比，m-amph 增加了假手术组 NAc 中的 DA 再摄取时间，LFS 和 HFS 均能阻断这种改变。LFS 还能降低与基线相比的相位 DA 释放。LFS 能够增加 NAc 中的多巴胺转运蛋白（DAT）表达。
这些结果表明，VTA 的 LFS 和 HFS DBS 均具有抗躁狂作用，并调节 NAc 中的 DA 动力学。更具体地说，DAT 表达增加导致的 DA 再摄取增加可能是 VTA DBS 发挥抗躁狂作用的潜在机制。
