Dataset Information

A novel V1a receptor antagonist blocks vasopressin-induced changes in the CNS response to emotional stimuli: an fMRI study.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusion

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.

SUBMITTER: Lee RJ

PROVIDER: S-EPMC3859978 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Over the past two decades, evidence has accumulated that the human amygdala exerts some of its functions also when the observer is not aware of the content, or even presence, of the triggering emotional stimulus. Nevertheless, there is as of yet no consensus on the limits and conditions that affect the extent of amygdala's response without focused attention or awareness. Here we review past and recent studies on this subject, examining neuroimaging literature on healthy participants as well as brain-damaged patients, and we comment on their strengths and limits. We propose a theoretical distinction between processes involved in attentional unawareness, wherein the stimulus is potentially accessible to enter visual awareness but fails to do so because attention is diverted, and in sensory unawareness, wherein the stimulus fails to enter awareness because its normal processing in the visual cortex is suppressed. We argue this distinction, along with data sampling amygdala responses with high temporal resolution, helps to appreciate the multiplicity of functional and anatomical mechanisms centered on the amygdala and supporting its role in non-conscious emotion processing. Separate, but interacting, networks relay visual information to the amygdala exploiting different computational properties of subcortical and cortical routes, thereby supporting amygdala functions at different stages of emotion processing. This view reconciles some apparent contradictions in the literature, as well as seemingly contrasting proposals, such as the dual stage and the dual route model. We conclude that evidence in favor of the amygdala response without awareness is solid, albeit this response originates from different functional mechanisms and is driven by more complex neural networks than commonly assumed. Acknowledging the complexity of such mechanisms can foster new insights on the varieties of amygdala functions without awareness and their impact on human behavior.