Clinical Neurosciences and Psychopharmacology Research Unit, Department of Psychiatry and Behavioral Neurosciences, The University of Chicago Chicago IL, USA.
Azevan Pharmaceuticals, Inc. Bethlehem, PA, USA ; Department of Biological Sciences, Lehigh University Bethlehem, PA, USA.
Front Syst Neurosci. 2013 Dec 12;7:100. doi: 10.3389/fnsys.2013.00100. eCollection 2013.
We hypothesized that SRX246, a vasopressin V1a receptor antagonist, blocks the effect of intranasally administered vasopressin on brain processing of angry Ekman faces. An interaction of intranasal and oral drug was predicted in the amygdala.
Twenty-nine healthy male subjects received a baseline fMRI scan while they viewed angry faces and then were randomized to receive oral SRX246 (120 mg PO twice a day) or placebo. After an average of 7 days of treatment, they were given an acute dose of intranasal vasopressin (40 IU) or placebo and underwent a second scan. The primary outcome was BOLD activity in the amygdala in response to angry faces. Secondary analyses were focused on ROIs in a brain regions previously linked to vasopressin signaling.
In subjects randomized to oral placebo-intranasal vasopressin, there was a significantly diminished amygdala BOLD response from the baseline to post-drug scan compared with oral placebo-intranasal placebo subjects. RM-ANOVA of the BOLD signal changes in the amygdala revealed a significant oral drug × intranasal drug × session interaction (F (1, 25) = 4.353, p < 0.05). Follow-up tests showed that antagonism of AVPR1a with SRX246 blocked the effect of intranasal vasopressin on the neural response to angry faces. Secondary analyses revealed that SRX246 treatment was associated with significantly attenuated BOLD responses to angry faces in the right temporoparietal junction, precuneus, anterior cingulate, and putamen. Exploratory analyses revealed that the interactive and main effects of intranasal vasopressin and SRX246 were not seen for happy or neutral faces, but were detected for aversive faces (fear + anger) and at a trend level for fear faces.
We found confirmatory evidence that SRX246 has effects on the amygdala that counter the effects of intranasal vasopressin. These effects were strongest for angry faces, but may generalize to other emotions with an aversive quality.
我们假设 SRX246，一种加压素 V1a 受体拮抗剂，可阻断鼻内给予加压素对大脑处理愤怒埃克曼面部的影响。预计在杏仁核中存在鼻内和口服药物的相互作用。
29 名健康男性受试者在观看愤怒面孔时接受基线 fMRI 扫描，然后随机接受口服 SRX246（每天两次，120mg PO）或安慰剂。经过平均 7 天的治疗后，他们接受了一次急性鼻内加压素（40IU）或安慰剂剂量，并进行了第二次扫描。主要结果是杏仁核对愤怒面孔的 BOLD 活性。次要分析集中在先前与加压素信号相关的脑区的 ROI 上。
在接受口服安慰剂-鼻内加压素随机分组的受试者中，与口服安慰剂-鼻内安慰剂组相比，从基线到药物后扫描，杏仁核的 BOLD 反应明显减弱。杏仁核 BOLD 信号变化的 RM-ANOVA 显示，口服药物×鼻内药物×会话的交互作用有显著差异（F（1，25）=4.353，p<0.05）。随访测试表明，SRX246 拮抗 AVPR1a 阻断了鼻内加压素对愤怒面孔神经反应的影响。进一步的分析表明，SRX246 治疗与右颞顶联合区、后扣带回、前扣带回和壳核对愤怒面孔的 BOLD 反应明显减弱有关。探索性分析表明，鼻内加压素和 SRX246 的交互和主要作用不仅见于快乐或中性面孔，而且见于厌恶面孔（恐惧+愤怒），并且在恐惧面孔上也呈趋势水平。
我们发现了证实性证据，表明 SRX246 对杏仁核有影响，可抵消鼻内加压素的作用。这些作用在愤怒面孔中最强，但可能扩展到具有厌恶性质的其他情绪。
