Predator odor-evoked BOLD activation in the awake rat: Modulation by oxytocin and V1a vasopressin receptor antagonists

Abstract

Modulators of unconditioned fear are potential targets for developing treatments for anxiety disorders. We used blood oxygen level dependent (BOLD) MRI to investigate the pattern of brain activity during the presentation of a predator odor (cat fur) and a repulsive novel odor, butyric acid (BA), to awake rats. We further tested whether odor-evoked BOLD activation involved oxytocin (OT) and vasopressin V1a receptors. Animals were subdivided into groups either administered an intracerebroventricular injection of artificial cerebrospinal fluid (CSF), an OT receptor antagonist or a V1a antagonist (125ng/10μL each) 90min before studies. BA odor evoked robust brain activation across olfactory, sensory, memory and limbic regions. The magnitude of BOLD activation across these regions was greater for BA than with cat fur. However, blockade of OT and V1a receptors differentially modulated odor evoked neural activity, particularly in the amygdala. OT and V1a antagonism preferentially modulated BOLD responding to BA in the cortical amygdala. While, OT and V1a antagonisms preferentially modulated BOLD responding to cat fur in the central amygdala. The data suggest that although OT receptors modulate BOLD activation in response to a novel and repulsive odor such as BA, vasopressin V1a receptors exert a modulatory influence on the neural response to a predator odor.