Neuropsychopharmacology & Psychobiology Research Group, University of Cádiz, Cádiz, Spain; CIBER of Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain.
CIBER of Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigación e Innovación en Ciencias Biomédicas de Cádiz, INiBICA, Hospital Universitario Puerta del Mar, Cádiz, Spain; Neuropsychopharmacology & Psychobiology Research Group, Department of Psychology, Area of Psychobiology, University of Cádiz, Puerto Real, Cádiz, Spain.
Brain Stimul. 2018 Jan-Feb;11(1):222-230. doi: 10.1016/j.brs.2017.10.003. Epub 2017 Oct 13.
Deep Brain Stimulation (DBS) of the subgenual cingulate cortex (SCC) is a promising therapeutic alternative to treat resistant major depressive disorder. In preclinical studies, DBS of the ventromedial prefrontal cortex (vmPFC, the rodent SCC correlate) provokes an antidepressant-like effect, along with changes in noradrenaline levels at the site of stimulation. Hence, DBS appears to activate the noradrenergic-locus coeruleus (LC) system.
OBJECTIVE/HYPOTHESIS: The aim of this study was to evaluate the effect of vmPFC DBS on the electrical activity of noradrenergic LC neurons, cortical oscillations and coherence between both brain areas in male rats.
The antidepressant-like effect of vmPFC DBS was evaluated through the forced swimming test. Tonic and evoked activity of LC neurons, LC activity of alpha2-adrenoceptors, local field potentials from LC and electrocorticogram signals were studied after DBS by electrophysiological recordings in anaesthetized rats. The effect of DBS on tyrosine hydroxylase (TH), noradrenaline transporters (NAT), phosphorylation of the extracellular signal-regulated kinase (ERK) and corticotropin releasing factor (CRF) expression in the LC were measured by western blot assays.
DBS induced an antidepressant-like effect increasing climbing behaviour in the FST that was accompanied by a robust increase of TH expression in the rat LC. The tonic and evoked activity of LC neurons was enhanced by DBS, which impaired alpha2-adrenoceptors activity. DBS also promoted an increase in slow LC oscillations, as well as a shift in LC-cortical coherence.
DBS of the vmPFC appears to affect the LC, producing changes that may underlie its antidepressant-like effects.
内侧眶额皮层（SCC）的深部脑刺激（DBS）是治疗难治性重度抑郁症的一种很有前途的治疗选择。在临床前研究中，腹内侧前额叶皮层（vmPFC，啮齿动物 SCC 的对应物）的 DBS 引发了抗抑郁样效应，同时刺激部位的去甲肾上腺素水平也发生了变化。因此，DBS 似乎激活了去甲肾上腺素能蓝斑核（LC）系统。
目的/假设：本研究旨在评估 vmPFC DBS 对雄性大鼠 LC 神经元电活动、皮质振荡以及两个脑区之间相干性的影响。
通过强迫游泳试验评估 vmPFC DBS 的抗抑郁样作用。在麻醉大鼠的电生理记录中，研究了 DBS 后 LC 神经元的紧张性和诱发性活动、LC 中的α2-肾上腺素能受体活动、LC 局部场电位和脑电信号。通过 Western blot 检测 LC 中的酪氨酸羟化酶（TH）、去甲肾上腺素转运体（NAT）、细胞外信号调节激酶（ERK）磷酸化和促肾上腺皮质释放因子（CRF）的表达，来测量 DBS 的作用。
DBS 诱导了抗抑郁样作用，增加了 FST 中的攀爬行为，同时伴随着大鼠 LC 中 TH 表达的显著增加。LC 神经元的紧张性和诱发性活动被 DBS 增强，这削弱了α2-肾上腺素能受体的活性。DBS 还促进了 LC 慢振荡的增加，以及 LC-皮质相干性的转移。
vmPFC 的 DBS 似乎会影响 LC，产生的变化可能是其抗抑郁样作用的基础。
