LAUSR

BACKGROUND There is growing evidence for a role of abnormal gut-brain signaling in disorders involving altered mood and affect, including depression. Studies using vagus nerve stimulation (VNS) suggest that the disruption of vagal afferent signaling may contribute to these abnormalities. To test this hypothesis, we used a rat model of subdiaphragmatic vagal deafferentation (SDA), the most complete and selective vagal deafferentation method existing to date, to study the consequences of complete disconnection of abdominal vagal afferents on affective behaviors. METHODS SDA- and Sham-operated male rats were subjected to several tests that are commonly used in preclinical rodent models to assess the presence of anhedonic behavior, namely the novel object-induced exploration test, the novelty-suppressed eating test, and the sucrose preference test. In addition, we compared SDA and Sham rats in a social interaction test and the forced swim test to assess sociability and behavioral despair, respectively. RESULTS Compared to Sham controls, SDA rats consistently displayed signs of anhedonic behavior in all test settings used. SDA rats also showed increased immobility and reduced swimming in the forced swim test, whereas they did not differ from Sham controls with regards to social approach behavior. LIMITATIONS This study was conducted in male rats only. Hence, possible sex-specific effects of SDA on affective behaviors remained unexamined. CONCLUSIONS Our findings demonstrate that hedonic behavior and behavioral despair are subject to visceral modulation through abdominal vagal afferents. These data are compatible with preclinical models and clinical trials showing beneficial effects of VNS on depression-like and affective behaviors.