Luyck K, Tambuyzer T, Deprez M, Rangarajan J, Nuttin B, Luyten L
Division of Experimental Neurosurgery and Neuroanatomy, KU Leuven, Leuven, Belgium.
Division of Animal and Human Health Engineering, KU Leuven, Leuven, Belgium.
Transl Psychiatry. 2017 Feb 14;7(2):e1033. doi: 10.1038/tp.2017.2.
We recently showed that deep brain stimulation (DBS) in the bed nucleus of the stria terminalis (BST) reduces obsessions, compulsions and associated anxiety in patients suffering from severe, treatment-refractory obsessive-compulsive disorder. Here, we investigated the anxiolytic effects of electrical BST stimulation in a rat model of conditioned anxiety, unrelated to obsessions or compulsions. Two sets of stimulation parameters were evaluated. Using fixed settings at 100 Hz, 40 μs and 300 μA (Set A), we observed elevated freezing and startle levels, whereas stimulation at 130 Hz, 220 μs and individually tailored amplitudes (Set B) appeared to reduce freezing. In a follow-up experiment, we evaluated the anxiolytic potential of Set B more extensively, by adding a lesion group and an additional day of stimulation. We found that electrical stimulation significantly reduced freezing, but not to the same extent as lesions. Neither lesions nor stimulation of the BST affected motor behavior or unconditioned anxiety in an open-field test. In summary, electrical stimulation of the BST was successful in reducing contextual anxiety in a rat model, without eliciting unwanted motor effects. Our findings underline the therapeutic potential of DBS in the BST for disorders that are hallmarked by pathological anxiety. Further research will be necessary to assess the translatability of these findings to the clinic.
我们最近发现,对终纹床核(BST)进行深部脑刺激(DBS)可减轻重度、难治性强迫症患者的强迫观念、强迫行为及相关焦虑。在此,我们在与强迫观念或强迫行为无关的条件性焦虑大鼠模型中研究了BST电刺激的抗焦虑作用。评估了两组刺激参数。使用100Hz、40μs和300μA的固定设置(A组)时,我们观察到僵住和惊吓水平升高,而以130Hz、220μs和个体化调整的幅度进行刺激(B组)似乎可降低僵住程度。在后续实验中,我们通过增加一个损伤组和额外一天的刺激,更广泛地评估了B组的抗焦虑潜力。我们发现电刺激显著降低了僵住程度,但程度不如损伤组。在旷场试验中,BST的损伤或刺激均未影响运动行为或非条件性焦虑。总之,BST电刺激成功降低了大鼠模型中的情境性焦虑,且未引发不必要的运动效应。我们的研究结果强调了BST区域DBS对以病理性焦虑为特征的疾病的治疗潜力。有必要进行进一步研究以评估这些发现向临床的可转化性。